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From September 25^th to 29^th, the 27th China Clinical Oncology Congress and the 2024 CSCO Annual Meeting were held in Xiamen. Experts and scholars in the field of oncology from all over China gathered together to discuss the hotspots at the forefront of clinical practice. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (“Kelun-Biotech”, 6990.HK) presented multiple clinical research results and progress of TROP2 ADC sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870) at the conference.

TNBC

                             【2024 CSCO：Oral report by Academician Binghe Xu 】

On the afternoon of September 27, Academician Binghe Xu from the Cancer Hospital of the Chinese Academy of Medical Sciences gave an oral presentation and paper discussion on the results of the Phase III OptiTROP-Breast01 study of sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC) in the Innovative Drugs Clinical Data Session.

The median PFS assessed by BICR was 6.7 months (95% CI, 5.5 to 8.0) with SKB264 and 2.5 months (95% CI, 1.7 to 2.7) with chemotherapy; The sac-TMT group had a 68% reduction in risk of disease progression or death compared to the chemotherapy group (HR 0.32; 95% CI, 0.22 to 0.44; P <0.00001). In the subset of pts with TROP2 H-score > 200, the median PFS was 8.3 months with SKB264 and 2.3 months with chemotherapy (HR 0.29; 95% CI, 0.19 to 0.46). The median OS was not reached (95% CI, 11.2 to NE) with SKB264 and 9.4 months (95% CI, 8.5 to 11.7) with chemotherapy. The sac-TMT group had a 47% reduction in risk of death compared to the chemotherapy group (HR 0.53; 95% CI, 0.36 to 0.78; P =0.00005). Compared to the investigator's choice of chemotherapy, sac-TMT for metastatic TNBC patients showed statistically and clinically significant improvements in PFS and OS, with a manageable safety profile, and could be a new and effective therapeutic option for this group of patients.

Binghe Xu said, “Breast cancer is a highly prevalent malignant tumor in the world, threatening women's lives and health, among which, triple-negative breast cancer is also known as ‘the most toxic’ breast cancer due to its poor therapeutic effect. The future direction of advanced triple-negative breast cancer treatment is precise and stratified treatment. Sac-TMT can help to meet more treatment needs of patients, and may be expected to become the new standard of second-line treatment for advanced triple-negative breast cancer in the future. For the research and development of ADC, domestic enterprises have gone through the stages of catching up and running parallel to each other, and now they have become an important force in the global ADC innovation technology, and we believe that one day, patients with advanced triple-negative breast cancer can get more effective treatment through ADC innovative drugs.”

NSCLC

【2024 CSCO：Oral report by Prof.Wengfeng Fang】

On the afternoon of September 28, Prof. Wenfeng Fang from the Affiliated Cancer Hospital of Sun Yat-sen University orally reported the results of the Phase II OptiTROP-Lung01study, a first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) with sac-TMT in combination with KL-A167, an anti-PD-L1 monoclonal antibody, in the session of Clinical Data of Innovative Drugs, with a paper discussion.

Pts with treatment naive advanced NSCLC without actionable genomic alterations were enrolled to receive SKB264 5 mg/kg Q3W + KL-A167 1200 mg Q3W (cohort 1A，130 Pts) or SKB264 5 mg/kg Q2W + KL-A167 900 mg Q2W (cohort 1B,133 Pts) in a non-randomized manner. After median follow up of 14.0 mo and 6.9 mo for cohort 1A and 1B, the ORR was 48.6% (18/37, 2 pending confirmation), DCR was 94.6% and median PFS was 15.4 mo (95% CI: 6.7, NE) with 6-mo PFS rate of 69.2% for cohort 1A ; the ORR was 77.6% (45/58, 5 pending confirmation), DCR was 100% and median PFS was not reached with 6-mo PFS rate of 84.6% for cohort 1B.

Prof. Wenfeng Fang said, “The emergence of ADC drugs is epoch-making. The dual-drug regimen of sac-TMT combined with immunotherapy is leading a new direction in the exploration of first-line treatment for advanced NSCLC, with very stunning efficacy observed in the preliminary study data. In the future, the potential for the application of sac-TMT in the treatment of NSCLC is worth looking forward to, and sac-TMT is expected to provide diversified treatment options and better survival benefits for more patients, both in the driver-negative and EGFR-mutated patient populations.”

CC

【2024 CSCO：Oral report by Pro.Jing Wang】

On the morning of September 28, Professor Jing Wang from Hunan Cancer Hospital orally reported the results of Efficacy and Safety of sac-TMT Plus Pembrolizumab in patients with recurrent or metastatic cervical cancer. Pts with R/M CC who had progressed on or after platinum-doublet chemotherapy and received no more than 2 systemic therapies for R/M disease were enrolled.38 pts were treated and followed up for at least 17 weeks or 2 tumor assessments. The median follow-up was 6.2 mo, The ORR was 57.9% (22/38, 3 unconfirmed), with 3 complete responses. Responses were also observed in pts were pre-treated with anti-PD-1 based therapy. Median PFS was not reached and 6-mo PFS rate was 65.7%.

Professor Jing Wang said, “Cervical cancer highly expresses TROP2, and previous studies have suggested that the overexpression ratio is more than 90%. High TROP2 expression is closely related to the poor prognosis of tumor patients, and it may also be related to the sensitivity of some drug therapies, which makes it a good target to explore. It is believed that with these promising results, more studies will emerge in the field of gynecologic oncology in the future to further validate these findings and bring hope to a wider range of cancer patients.”

EC/OC

【2024 CSCO：Oral report by Dr.Zhuo Yang】

On the morning of September 28, Dr. Zhuo Yang from Liaoning Provincial Cancer Hospital shared the results of safety and efficacy of sac-TMT in pts with previously treated advanced endometrial carcinoma (EC) and ovarian cancer (OC) from a Phase 2 Study. In the endometrial cancer cohort, 44 EC pts were enrolled and median follow-up time was 7.2 mo. 52.3% of pts had received ≥ 2 prior lines of therapy. The ORR was 34.1% (15/44, 12 confirmed) and DCR was 75%. Median PFS was 5.7 mo (95% CI: 3.7, 9.4) with 6-mo PFS rate of 47.5%.

40 OC pts were enrolled and median follow-up time was 28.2 mo. All pts had received ≥ 2 prior lines of therapy (80% of pts ≥ 3 prior lines). 87.5% of pts were platinum-resistant. The ORR was 40% (16/40, 14 confirmed) and DCR was 75%. mPFS was 6.0 mo (95% CI: 3.9, 7.3); mo was 16.5 mo (95% CI: 10.7, NE). In the pts with TROP2 IHC H-score > 200 (n=13) or H-score ≤ 200 (n=22), the ORR was 61.5% (8/13, 7 confirmed) and 27.3% (6/22, 6 confirmed) respectively. In the pts with platinum-resistant (n=35), mPFS was 6.0 mo (95% CI: 5.3, 7.3) and mOS was 16.1 mo (95% CI: 10.5, NE).

Prof Danbo Wang said, “Ovarian cancer and endometrial cancer have their own epidemiological characteristics, and the incidence rate of endometrial cancer in developed cities in China is increasing year by year, and it may become the top gynecological malignant tumor in Chinese women in the future. In contrast, ovarian cancer is characterized by insidious onset, high late detection rate and high mortality rate. Exploring new therapeutic strategies to overcome platinum resistance and improve the survival rate of ovarian cancer patients is a key direction for future research. Sac-TMT shows great potential in the treatment of advanced endometrial and ovarian cancers. It has not only achieved remarkable results in terms of efficacy, but also well controlled safety. I believe that in the future research and application, it will become a leader in the field of ADC innovative drug development and bring new hope to more gynecological oncology patients.”

With a caring heart, Kelun-Biotech is committed to solving unmet clinical needs in China and around the world. By focusing on its own technological strengths, Kelun-Biotech is able to provide patients in China with novel ADC drugs with significant clinical value and excellent cost-effectiveness, and to enhance the benefits for clinical patients. In the future, we will continue to accelerate the R&D and clinical progress of our drug candidates, enhance our integrated drug development capabilities, and contribute to the realization of Healthy China 2030.

From September 25^th to 29^th, the 27th China Clinical Oncology Congress and the 2024 CSCO Annual Meeting were held in Xiamen. Experts and scholars in the field of oncology from all over China gathered together to discuss the hotspots at the forefront of clinical practice. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (“Kelun-Biotech”, 6990.HK) presented multiple clinical research results and progress of TROP2 ADC sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870) at the conference.

TNBC

                             【2024 CSCO：Oral report by Academician Binghe Xu 】

On the afternoon of September 27, Academician Binghe Xu from the Cancer Hospital of the Chinese Academy of Medical Sciences gave an oral presentation and paper discussion on the results of the Phase III OptiTROP-Breast01 study of sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC) in the Innovative Drugs Clinical Data Session.

The median PFS assessed by BICR was 6.7 months (95% CI, 5.5 to 8.0) with SKB264 and 2.5 months (95% CI, 1.7 to 2.7) with chemotherapy; The sac-TMT group had a 68% reduction in risk of disease progression or death compared to the chemotherapy group (HR 0.32; 95% CI, 0.22 to 0.44; P <0.00001). In the subset of pts with TROP2 H-score > 200, the median PFS was 8.3 months with SKB264 and 2.3 months with chemotherapy (HR 0.29; 95% CI, 0.19 to 0.46). The median OS was not reached (95% CI, 11.2 to NE) with SKB264 and 9.4 months (95% CI, 8.5 to 11.7) with chemotherapy. The sac-TMT group had a 47% reduction in risk of death compared to the chemotherapy group (HR 0.53; 95% CI, 0.36 to 0.78; P =0.00005). Compared to the investigator's choice of chemotherapy, sac-TMT for metastatic TNBC patients showed statistically and clinically significant improvements in PFS and OS, with a manageable safety profile, and could be a new and effective therapeutic option for this group of patients.

Binghe Xu said, “Breast cancer is a highly prevalent malignant tumor in the world, threatening women's lives and health, among which, triple-negative breast cancer is also known as ‘the most toxic’ breast cancer due to its poor therapeutic effect. The future direction of advanced triple-negative breast cancer treatment is precise and stratified treatment. Sac-TMT can help to meet more treatment needs of patients, and may be expected to become the new standard of second-line treatment for advanced triple-negative breast cancer in the future. For the research and development of ADC, domestic enterprises have gone through the stages of catching up and running parallel to each other, and now they have become an important force in the global ADC innovation technology, and we believe that one day, patients with advanced triple-negative breast cancer can get more effective treatment through ADC innovative drugs.”

NSCLC

【2024 CSCO：Oral report by Prof.Wengfeng Fang】

On the afternoon of September 28, Prof. Wenfeng Fang from the Affiliated Cancer Hospital of Sun Yat-sen University orally reported the results of the Phase II OptiTROP-Lung01study, a first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) with sac-TMT in combination with KL-A167, an anti-PD-L1 monoclonal antibody, in the session of Clinical Data of Innovative Drugs, with a paper discussion.

Pts with treatment naive advanced NSCLC without actionable genomic alterations were enrolled to receive SKB264 5 mg/kg Q3W + KL-A167 1200 mg Q3W (cohort 1A，130 Pts) or SKB264 5 mg/kg Q2W + KL-A167 900 mg Q2W (cohort 1B,133 Pts) in a non-randomized manner. After median follow up of 14.0 mo and 6.9 mo for cohort 1A and 1B, the ORR was 48.6% (18/37, 2 pending confirmation), DCR was 94.6% and median PFS was 15.4 mo (95% CI: 6.7, NE) with 6-mo PFS rate of 69.2% for cohort 1A ; the ORR was 77.6% (45/58, 5 pending confirmation), DCR was 100% and median PFS was not reached with 6-mo PFS rate of 84.6% for cohort 1B.

Prof. Wenfeng Fang said, “The emergence of ADC drugs is epoch-making. The dual-drug regimen of sac-TMT combined with immunotherapy is leading a new direction in the exploration of first-line treatment for advanced NSCLC, with very stunning efficacy observed in the preliminary study data. In the future, the potential for the application of sac-TMT in the treatment of NSCLC is worth looking forward to, and sac-TMT is expected to provide diversified treatment options and better survival benefits for more patients, both in the driver-negative and EGFR-mutated patient populations.”

CC

【2024 CSCO：Oral report by Pro.Jing Wang】

On the morning of September 28, Professor Jing Wang from Hunan Cancer Hospital orally reported the results of Efficacy and Safety of sac-TMT Plus Pembrolizumab in patients with recurrent or metastatic cervical cancer. Pts with R/M CC who had progressed on or after platinum-doublet chemotherapy and received no more than 2 systemic therapies for R/M disease were enrolled.38 pts were treated and followed up for at least 17 weeks or 2 tumor assessments. The median follow-up was 6.2 mo, The ORR was 57.9% (22/38, 3 unconfirmed), with 3 complete responses. Responses were also observed in pts were pre-treated with anti-PD-1 based therapy. Median PFS was not reached and 6-mo PFS rate was 65.7%.

Professor Jing Wang said, “Cervical cancer highly expresses TROP2, and previous studies have suggested that the overexpression ratio is more than 90%. High TROP2 expression is closely related to the poor prognosis of tumor patients, and it may also be related to the sensitivity of some drug therapies, which makes it a good target to explore. It is believed that with these promising results, more studies will emerge in the field of gynecologic oncology in the future to further validate these findings and bring hope to a wider range of cancer patients.”

EC/OC

【2024 CSCO：Oral report by Dr.Zhuo Yang】

On the morning of September 28, Dr. Zhuo Yang from Liaoning Provincial Cancer Hospital shared the results of safety and efficacy of sac-TMT in pts with previously treated advanced endometrial carcinoma (EC) and ovarian cancer (OC) from a Phase 2 Study. In the endometrial cancer cohort, 44 EC pts were enrolled and median follow-up time was 7.2 mo. 52.3% of pts had received ≥ 2 prior lines of therapy. The ORR was 34.1% (15/44, 12 confirmed) and DCR was 75%. Median PFS was 5.7 mo (95% CI: 3.7, 9.4) with 6-mo PFS rate of 47.5%.

40 OC pts were enrolled and median follow-up time was 28.2 mo. All pts had received ≥ 2 prior lines of therapy (80% of pts ≥ 3 prior lines). 87.5% of pts were platinum-resistant. The ORR was 40% (16/40, 14 confirmed) and DCR was 75%. mPFS was 6.0 mo (95% CI: 3.9, 7.3); mo was 16.5 mo (95% CI: 10.7, NE). In the pts with TROP2 IHC H-score > 200 (n=13) or H-score ≤ 200 (n=22), the ORR was 61.5% (8/13, 7 confirmed) and 27.3% (6/22, 6 confirmed) respectively. In the pts with platinum-resistant (n=35), mPFS was 6.0 mo (95% CI: 5.3, 7.3) and mOS was 16.1 mo (95% CI: 10.5, NE).

Prof Danbo Wang said, “Ovarian cancer and endometrial cancer have their own epidemiological characteristics, and the incidence rate of endometrial cancer in developed cities in China is increasing year by year, and it may become the top gynecological malignant tumor in Chinese women in the future. In contrast, ovarian cancer is characterized by insidious onset, high late detection rate and high mortality rate. Exploring new therapeutic strategies to overcome platinum resistance and improve the survival rate of ovarian cancer patients is a key direction for future research. Sac-TMT shows great potential in the treatment of advanced endometrial and ovarian cancers. It has not only achieved remarkable results in terms of efficacy, but also well controlled safety. I believe that in the future research and application, it will become a leader in the field of ADC innovative drug development and bring new hope to more gynecological oncology patients.”

With a caring heart, Kelun-Biotech is committed to solving unmet clinical needs in China and around the world. By focusing on its own technological strengths, Kelun-Biotech is able to provide patients in China with novel ADC drugs with significant clinical value and excellent cost-effectiveness, and to enhance the benefits for clinical patients. In the future, we will continue to accelerate the R&D and clinical progress of our drug candidates, enhance our integrated drug development capabilities, and contribute to the realization of Healthy China 2030.

[Sep 9^th] The European Society for Medical Oncology (ESMO) Congress 2024 to be held in Barcelona, Spain from September 13 to 17, 2024. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd（“Kelun-Biotech”）will present the following results of its anti-TROP2 ADC sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870).

1.Efficacy and safety of sac-TMT plus pembrolizumab (KEYTRUDA®) in patients with recurrent or metastatic cervical cancer (CC), to be presented in a mini oral session on September 15, 2024, 14:55-15:00, local time (presentation number: 716MO);

2.Safety and efficacy of sac-TMT monotherapy in patients with previously treated advanced endometrial carcinoma (EC) and ovarian cancer (OC) from a phase 2 study, to be presented in a mini oral session on September 15, 2024, 14:50-14:55, local time (presentation number: 715MO); 

3.Exploratory analysis of patients with or without prior PD-(L)1 inhibitors in phase 3 OptiTROP-Breast01 study of sac-TMT versus chemotherapy for previously treated advanced triple-negative breast cancer (TNBC), to be presented as a poster on September 16, 2024, local time (presentation number: 386P).

The abstracts for the above studies were published on the official website of the ESMO Congress on September 9, 2024, local time. The study results are summarized as follows:

CC

Patients with recurrent or metastatic (R/M) CC who had progressed on or after platinum-doublet chemotherapy and received no more than 2 systemic therapies (PD-(L)1 inhibitor allowed) for R/M disease were enrolled in this study. Sac-TMT at 3 or 5 mg/kg Q2W plus pembrolizumab at 400 mg Q6W was assessed in safety run-in period and the doses deemed well tolerated were explored in expansion period.

As of data cutoff of March 25, 2024, 38 patients were treated and followed up for at least 17 weeks or 2 tumor assessments (3 received sac-TMT at 3 mg/kg, 35 received sac-TMT at 5 mg/kg). The median follow-up was 6.2 months. The median age of patients was 52 years. 76.3% had squamous histology, 47.4% had received two prior lines of therapy, 52.6% had received bevacizumab, and 42.1% had received anti-PD-1-based therapy. The ORR was 57.9% (22/38, 19 (50%) confirmed), with 3 complete responses. Median duration of response (DoR) was not reached and the 6-month DoR rate was 82.1%. Responses were also observed in patients who were pre-treated with anti-PD-1 based therapy (ORR 68.8%, 11/16). Median PFS was not reached and the 6-month PFS rate was 65.7%.

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 47.4% of patients. The most common Grade ≥3 TRAEs were neutrophil count decreased (23.7%), anemia (21.1%) and white blood cell count decreased (15.8%). TRAEs led to dose reduction of sac-TMT in 44.7% of patients and discontinuation of sac-TMT in 1 pt (2.6%). No TRAEs led to discontinuation of both drugs.

A Phase 3 global study sponsored by MSD evaluating sac-TMT monotherapy versus treatment of physician’s choice (TPC) as second-line treatment for patients with recurrent or metastatic CC is ongoing (NCT06459180).

EC and OC

Two cohorts of patients with advanced EC and OC, respectively, who had previously been treated with platinum-based chemo were given sac-TMT at 5 mg/kg Q2W until disease progression, unacceptable toxicity or withdrawal of consent. The TROP2 expression was scored using the semi-quantitative H-score method, and cut-off point was set to 200.

As of data cutoff of March 5, 2024, 44 patients were enrolled to the EC cohort and median follow-up time was 7.2 months. 52.3% of patients had received ≥ 2 prior lines of therapy. The objective response rate (ORR) was 34.1% (15/44, 12 confirmed) and the disease control rate (DCR) was 75%. Median progression-free survival (PFS) was 5.7 months (95% CI: 3.7, 9.4) with 6-month PFS rate of 47.5%. For patients with TROP2 IHC H-score > 200 (n=12), the ORR was 41.7% (5/12, 3 confirmed) and for patients with an H-score ≤ 200 (n=28), the ORR was 35.7% (10/28, 9 confirmed). 40 patients were enrolled to the OC cohort and median follow-up time was 28.2 months. All patients had received ≥ 2 prior lines of therapy (with 80% of patients receiving ≥3 prior lines) and 87.5% of patients were platinum-resistant. The ORR was 40% (16/40, 14 confirmed) and DCR was 75%. Median PFS was 6.0 months (95% CI: 3.9, 7.3) and median overall survival (OS) was 16.5 months (95% CI: 10.7, NE). In patients with TROP2 IHC H-score > 200 (n=13), the ORR was 61.5% (8/13, 7 confirmed) and in patients with an H-score ≤ 200 (n=22), the ORR was 27.3% (6/22, 6 confirmed). In the patients who are platinum-resistant (n=35), median PFS was 6.0 months (95% CI: 5.3, 7.3) and median OS was 16.1 months (95% CI: 10.5, NE).

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 72.7% and 67.5% of patients with EC and OC, respectively. The most common Grade ≥3 TRAEs (≥15%) (EC and OC) were neutrophil count decreased (43.2% and 30.0%), white blood cell count decreased (40.9% and 22.5%), anemia (29.5% and 35.0%) and stomatitis (13.6% and 15.0%). TRAEs led to discontinuation in 1(2.3%) and 5(12.5%) patients with EC and OC, respectively.

A Phase 3 global study sponsored by MSD evaluating sac-TMT as a monotherapy for the treatment of EC who have received prior platinum-based chemotherapy and immunotherapy is ongoing (NCT06132958).

TNBC

Patients with locally recurrent or metastatic TNBC who had received ≥2 prior therapies, with at least one given in the metastatic setting, were randomized to receive either sac-TMT or treatment of physician’s choice (TPC: eribulin, capecitabine, gemcitabine, or vinorelbine). The primary endpoint was PFS by blinded independent central review (BICR).

As of Nov 30, 2023, 24.6% (32/130) of patients treated with sac-TMT had received prior PD-(L)1 inhibitors and 27.1% (36/133) treated with TPC had received prior PD-(L)1 inhibitors. Clinical benefit was observed with sac-TMT versus TPC in this subgroup. The median PFS by BICR was 5.6 months versus 2.7 months (HR 0.31; 95% CI 0.17-0.54), and ORR by BICR was 56.3% for those treated with sac-TMT versus 5.6% for those treated with TPC. For those patients who didn’t receive prior PD-(L)1 inhibitors, similar improvements in efficacy outcomes were observed with sac-TMT versus TPC. The median PFS was 7.2 versus 2.3 months (HR 0.34; 95% CI 0.23-0.48), and ORR was 41.8% versus 14.4%.

Safety data in the sac-TMT arm were similar between patients with prior or without prior PD-(L)1 inhibitor treatment.

The results from the Phase 3 OptiTROP-Breast01 study of sac-TMT in patients with previously treated locally recurrent or metastatic TNBC was presented on June 2, 2024 at the 2024 ASCO Annual Meeting, details of which may be found in the Company’s 2024 interim result announcement and announcement dated May 24, 2024.

A Phase 3 global study sponsored by MSD evaluating sac-TMT plus pembrolizumab versus TPC in patients with TNBC who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) (NCT06393374) and a Phase 3 study sponsored by the Company of sac-TMT in China for 1L treatment for patients with unresectable advanced, recurrent or metastatic TNBC whose tumors are PD-L1 negative or in patients whose tumors are PD-L1 positive and have relapsed after prior anti-PD-(L)1 inhibitor in early setting (NCT06279364) are both ongoing.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (which includes Mainland China, Hong Kong, Macao, and Taiwan). KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

The incidence rate of cervical cancer ranks first among the three major malignant tumors in gynecology, and is the fourth leading cause of cancer deaths among women. According to the “China Malignant Tumor Discipline Development Report (2023)”, the incidence of gynecological tumors in China continues to show an increasing trend, in which the number of annual incidence cases of cervical cancer is 119,300, and the number of annual death cases is 37,200 ^[1]. Endometrial cancer (EC), as the second common gynecological malignant tumor after cervical cancer (CC), accounts for 20% to 30% of gynecological malignant tumors, with 77,700 new cases and 13,500 deaths in China in 2022 ^[2]; surgery is the main treatment for endometrial cancer, and except for the patients who can not tolerate surgery or who can not be operated in advanced stages, they should be operated with the supplement of Radiation therapy, chemotherapy, hormone and immune-targeted therapy and other comprehensive treatments. In addition, as the third common gynecological malignant tumor, the incidence rate of ovarian cancer (OC) is also high, and the number of new patients with OC in China in 2022 was 61,100 ^[2], with the incidence rate ranking the third of female reproductive system tumors ^[3].

In addition to the above three common gynecological malignant tumors, breast cancer is also a threat to women's lives and health. Among them, triple-negative breast cancer has unique biobehavioral characteristics, and is also known as the “most toxic” breast cancer. 2022 analysis of China's malignant tumor epidemiology data shows that there are 357,000 new cases of breast cancer and 75,000 deaths in Chinese women annually ^[4]. In the absence of effective therapeutic targets for triple-negative breast cancer, chemotherapy is the most important systemic treatment in the clinic ^[5], but it often has poor efficacy and high toxicity and side effects, and the prognosis is different from other subtypes of breast cancer ^[6], so it is necessary to explore more therapeutic means to improve the clinical benefit.

The research results for different indications of sacituzumab tirumotecan (sac-TMT) announced at the ESMO Congress are expected to further meet the therapeutic needs of gynecological oncology including triple-negative breast cancer, and benefit more clinical patients.

Dr. Junyou Ge, Chief Ｅxecutive Officer of Kelun-Biotech, said, “Adhering to source innovation and possessing world-class innovation capabilities of our own are prerequisites for the sustainable development of innovative drug companies. We are very pleased that TROP2 ADC sacituzumab tirumotecan has demonstrated excellent clinical efficacy and safety in a number of studies in gynecologic oncology indications announced at the ESMO Congress. Kelun-Biotech has always been committed to solving unmet medical needs in China and around the world, with patients around the globe in mind, and with patient benefit as its primary goal. With a heart of love for patients, we look forward to providing patients around the world with innovative Chinese ADCs with significant clinical value and excellent cost-effectiveness.”

Reference

[1][China Malignant Tumor Discipline Development Report (2023)].

[2] Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Center. 2024;4(1).
[3] Ovarian Cancer datamonitor.
[4].Han, Bingfeng, et al. "Cancer incidence and mortality in China, 2022." Journal of the National Cancer Center 4.1 (2024): 47-53.   

[5]. [Chinese Society of Clinical Oncology (CSCO) (2024)] Guidelines for the diagnosis and treatment of breast cancer.

[6]. https://seer.cancer.gov/statfacts/html/breast-subtypes.html .

On August 20, the new drug application (NDA) for the core product sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870) based on the positive results from the pivotal OptiTROP-Lung03 study has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (“Kelun-Biotech”, 6990.HK)

OptiTROP-Lung03 is a multi-center, randomized, pivotal clinical study that evaluates sac-TMT monotherapy 5mg/kg every other week (Q2W) as an intravenous injection versus docetaxel for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who failed after treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy. At a pre-specified analysis, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR) and progression-free survival (PFS) compared with docetaxel.

Lung cancer mainly includes non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which NSCLC is the most common pathological type, accounting for about 80%-85% of all lung cancers. The molecular typing of NSCLC patients in China is different from that of Western populations, and EGFR mutation is a common variant gene type, accounting for about 40%-50% of lung adenocarcinoma patients in China ^[1]. According to the 2024 CSCO guidelines, EGFR-TKIs are the preferred treatment for stage IV EGFR-mutant NSCLC ^[2]; platinum-containing chemotherapy is the main first-line chemotherapy regimen after resistance to EGFR-TKIs; and existing treatment regimens are ineffective in those who have failed EGFR-TKIs and platinum-containing chemotherapy. Single-agent chemotherapy is the current standard of care for this population, and docetaxel is the most commonly used single-agent chemotherapy, with an ORR of 3.2%-10.8%, a median PFS of only about 2 months, and a median OS of about 6-8 months ^[3,4,5,6,7]. For patients with locally advanced or metastatic EGFR-mutated NSCLC who have failed treatment with EGFR-TKIs and who have failed platinum-containing chemotherapy, the existing treatment regimens are less efficacious, there is a large unmet clinical need, and new drugs are urgently needed to improve patient survival.

Kelun-Biotech has filed the Application for sac-TMT for injection for the treatment of patients with locally advanced or metastatic EGFR-mutant NSCLC who failed after treatment with an EGFR-TKI and platinum-based chemotherapy.

The Application is the second NDA for sac-TMT that has been accepted by the NMPA. On August14, 2024, it was announced on the official website of the CDE that the Application was plannedto be included in the priority review and approval process of the CDE. Previously, an NDA for sac-TMT in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) was accepted by the NMPA.

Dr. Junyou Ge, CEO of Kelun-Biotech, said, “It is a great honor to have the second NDA of SKB264 accepted. Kelun-Biotech has always adhered to an innovation-driven development strategy, actively exploring cutting-edge technologies and new approaches to the treatment of major diseases. In response to unmet medical needs, we are committed to the original innovation of new drugs with differentiated advantages and international potential. By enhancing our end-to-end innovative drug development capabilities, we continuously improve the efficiency and success rate of drug research and development, and make every effort to move forward our clinical research progress. We are dedicated to continuously exploring and rapidly validating the clinical value of core projects. The company will always be guided by a caring heart, striving for excellence, and contributing to the great global oncology health cause.”

About Kelun-Biotech

Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs.

At present, the Company has more than 30 ongoing innovative projects in major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, including over 10 projects in the clinical stage and 4 projects in the NDA stage with several global trials being conducted simultaneously in multiple countries, including China, Europe, and the United States. The company has established one of the world’s leading proprietary ADC platforms, OptiDC?, and has 5 ADC projects in the clinical stage (2 of which are in the NDA stage) and several projects in the preclinical stage. For more information, please visit https://kelun-biotech.com/.

References:

[1] [Chinese Society of Clinical Oncology (CSCO)(2024)] Guidelines for the diagnosis and treatment of non-small cell lung cancer.

[2] [Chinese Society of Clinical Oncology (CSCO)(2024)] Guidelines for the diagnosis and treatment of non-small cell lung cancer.

[3] Hanna N,Shepherd FA, Fossella Fv, et al.(2004)

[4] Randomized Phase lll Trial of Pemetrexed, versus Docetaxel in Patients with Non-Small-Cell Lung CancerPreviously Treated with Chemotherapy.Journa otClcaOncology,22:1589-1597.

[5] Jyoti D. Patel, Mleng J, et al. (2023) Clinical charateristics, real-world treatment patterns, and clinicaloutcomes among patients with previously treated metastatic or unresectable EGFR-mutated non-small cellung cancer in the United States. Cancer Research.83:6754.

[6] KawaguchiT, Ando M. Asami K, et a. 2014) Randomized phase ll trlal of erlotnib versus docetaxe assecond- or third-line therapy in patients with advanced non-small-cell lung cancer. Docetaxel and Erlotinibung Cancerlra (DEhA)Journa of cinica32(18):1902-1908.

[7] Krzakowski M, Ramlau R, Jassem J, et al. (2010)] Phase Ⅲ trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. Journal of Clinical Oncology, 28(1.

("Kelun-Biotech" or the "Company", SEHK: 6990.HK) announces that the Company has received a Notice of Clinical Trial Approval (IND) for SKB518, an innovative ADC drug developed by the Company, in patients with advanced solid tumors from the Center for Drug Evaluation (CDE) of the State Drug Administration (NDA). (CDE) of the National Drug Administration (NMPA) for the approval of the clinical trial application (IND) of SKB518 for injection, an innovative ADC drug developed by the Company, to conduct clinical trials in patients with advanced solid tumors.

SKB518 for injection is an innovative antibody-coupled drug with proprietary intellectual property rights developed by the Company by utilizing the "OptiDC?" platform technology in light of the biological characteristics of the target site, and it has demonstrated good efficacy and safety window in the preclinical stage.

Dr. Junyou Ge, Chief Ｅxecutive Officer of Kelun-Biotech, said, "The entry of SKB518 into clinical trials enriches Kelun-Biotech's clinical product portfolio in the field of oncology ADC therapeutics, and paves a broader path for the company's flexible development of future pipelines in the oncology field. We are simultaneously accelerating the independent research and development of more than 10 preclinical-stage ADCs and novel coupling technology drug assets, and this year we plan to continue to file clinical INDs for a number of preclinical ADC pipelines."

About Kelun-Biotech

Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs.

At present, the Company has more than 30 ongoing innovative projects in major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, including over 10 projects in the clinical stage and 4 projects in the NDA stage with several global trials being conducted simultaneously in multiple countries, including China, Europe, and the United States. The company has established one of the world’s leading proprietary ADC platforms, OptiDC?, and has 5 ADC projects in the clinical stage (2 of which are in the NDA stage) and several projects in the preclinical stage. For more information, please visit https://kelun-biotech.com/.

 (May 24th, Chengdu and New Jersey) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting to be held in Chicago, Illinois, the United States of America from May 31 to June 4, 2024, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the “Company”) will present two clinical stage study results at ASCO.

1.The Phase 3 OptiTROP-Breast01 study of its anti-TROP2 ADC sacituzumab tirumotecan (sac-TMT) (formerly SKB264/MK-2870) in patients with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC).

?   Session: Special clinical science symposium (Abstract #104; Next-Generation Antibody–Drug Conjugates: The Revolution Continues),

?   Time:  June 2, 2024, 9:45 AM to 11:15 AM local time

2.  The Phase 2 OptiTROP-Lung01 study of sac-TMT in combination with KL-A167 (an anti-PD-L1 mAb) as 1L treatment for patients with advanced non-small cell lung cancer (NSCLC)

?   Session: oral (Abstract #8502; Lung Cancer—Non-Small Cell Metastatic Oral)

?   Time: May 31, 2024, 2:45 PM to 5:45 PM local time.

Sac-TMT is jointly developed by Kelun-Biotech and MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) at clinical stage.

The abstracts for the above studies were published on ASCO’s official website on [May 23, 2024], local time. The study results are summarized as follows:

TNBC

Patients were randomly assigned (1:1) to receive sac-TMT (n = 130) or chemotherapy (n = 133). The median age was 51 years; 87% had visceral metastases; 26% received prior PD-1/PD-L1 inhibitors; 48% received three or more prior lines of chemotherapy for advanced disease. The primary endpoint of progression free survival (PFS) was met based on interim analysis (data cut-off: Jun 21, 2023) with a 69% reduction in risk of progression or death (HR 0.31; 95% CI, 0.22 to 0.45; P <0.00001).

The median PFS, as assessed by BICR, was 5.7 months (95% CI, 4.3 to 7.2) with sac-TMT and 2.3 months (95% CI, 1.6 to 2.7) with chemotherapy; PFS rate at 6 months was 43.4% vs 11.1%. In the subset of patients with trophoblast cell-surface antigen 2 (TROP2) H-score > 200, the median PFS was 5.8 months with sac-TMT and 1.9 months with chemotherapy (HR 0.28; 95% CI, 0.17 to 0.48). At the first planned interim analysis for overall survival (OS) (data cut-off: Nov 30, 2023) with median follow-up of 10.4 months, OS was statistically significant in favor of sac-TMT (HR 0.53; 95% CI, 0.36 to 0.78; P =0.0005); the median OS was not reached (95% CI, 11.2 to NE) with sac-TMT and 9.4 months (95% CI, 8.5 to 11.7) with chemotherapy. The objective response rate (ORR) assessed by BICR was 43.8% with sac-TMT and 12.8% with chemotherapy.

Most common grade ≥ 3 treatment-related adverse events (TRAEs) (sac-TMT vs. chemotherapy) were neutrophil count decreased (32.3% vs. 47.0%), anemia (27.7% vs. 6.1%) and white blood cell count (WBC) decreased (25.4% vs. 36.4%).

A Phase 3 global study led by MSD of sac-TMT plus pembrolizumab versus treatment of physician's choice (TPC) in TNBC who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery (NCT06393374) and a Phase 3 study led by the Company of sac-TMT in China for 1L treatment of unresectable locally advanced, recurrent or metastatic PD-L1 negative TNBC (NCT06279364) are ongoing.

NSCLC

Patients with treatment naive advanced NSCLC without actionable genomic alterations were enrolled to receive sac-TMT 5 mg/kg Q3W plus KL-A167 1200 mg Q3W (cohort 1A) or sac-TMT 5 mg/kg Q2W plus KL-A167 900 mg Q2W (cohort 1B) in a non-randomized manner until disease progression or unacceptable toxicity. As of January 02, 2024, 40 and 63 patients have been enrolled in cohort 1A and 1B, respectively. Median ages were 63/63 years (cohort 1A/1B); 97.5%/85.7% had Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 1; 30.0%/33.3%, 32.5%/30.2% and 37.5%/36.5% of patients had programmed death ligand 1 (PD-L1) expression < 1%, 1%-49% and ≥ 50% of tumor cells by IHC 22C3 pharmDx assay, respectively.

After median follow up of 14.0 months for cohort 1A, the ORR was 48.6% (18/37, 2 pending confirmation), disease control rate (DCR) was 94.6% and median PFS was 15.4 months (95% CI: 6.7, NE) with a 6-month PFS rate of 69.2%. After median follow-up of 6.9 months for cohort 1B, the ORR was 77.6% (45/58, 5 pending confirmation), DCR was 100% and median PFS was not reached with a 6-month PFS rate of 84.6%. Additional subgroup analyses of cohort 1B are shown in the following table:

*Including confirmed or unconfirmed response. ORR was calculated based on response evaluable population defined as patients with ≥ 1 on-study scans.

In cohorts 1A and 1B, the most common Grade ≥ 3 TRAEs were neutrophil count decreased (30.0%/30.2%), WBC decreased (5.0%/17.5%), anemia (5.0%/15.9%), rash (5.0%/6.3%) and drug eruption (7.5%/0). Treatment-related adverse events leading to discontinuation of sac-TMT occurred in 1 patient of cohort 1B due to drug hypersensitivity, and there were no treatment-related deaths.

Two Phase 3 global studies led by MSD of sac-TMT in patients with 3L+ EGFR mutant NSCLC (NCT06074588), and 2L EGFR mutant NSCLC (NCT06305754) and a Phase 3 study led by the Company of sac-TMT in China in patients with 2L EGFR mutant NSCLC (NCT05870319) are ongoing. Additionally, Three Phase 3 global studies led by MSD of sac-TMT plus pembrolizumab are ongoing: One in patients with 1L Metastatic Squamous NSCLC (NCT06422143) , a second  in patients with metastatic NSCLC expressing PD-L1 ≥ 50% (NCT06170788), and the third in patients with resectable NSCLC not achieving a pathological complete response (NCT06312137) .

On May 16, 2024, Kelun Group celebrated the Group's twenty-eighth birthday. On the occasion of the 28th birthday of Kelun Group, Kelun-Biotech (6990.HK), together with Kelun Research Institute, honored the long-serving employees and celebrated with them. The "28 years of riding the wind together, I grow with Kelun" series of staff activities came to a successful conclusion.

Activity 1: "Cultural Symbiosis" Theme Activity

The "Cultural Symbiosis" activity began with the firm and powerful "Elite Oath" of 170 employees from 34 teams. In the "Culture Lecture - Side by Side - Culture Transmission - Working Together - Dedication to Factory Day" competition, colleagues within the team support each other to work together, the teams learn from each other to catch up with each other, in a pleasant and intense atmosphere to promote the corporate culture, enhance the team cohesion, and match the style of the people of Kelun!

                                                                                                         Highlights of the event

Activity 2: "All the Way" Long-term Service Employee Recognition Ceremony

To fight for the waves, a group of Kelun people have been working together with great expertise. In order to inspire and thank the long-serving employees of Kelun, on May 16th, the Group's birthday, Kelun-Biotech and Kelun Research Institute honored more than 40 employees who have joined Kelun Group for 15 years and above.

At the recognition ceremony, the company management presented each long-service employee with a certificate of honor and a souvenir. Employees are one of the most valuable assets of Kelun, they have traveled with Kelun all the way, not only witnessed the growth of the company, but also promoted the development of the company so far.

Kelun-Biotech also looks forward to more employees joining the ranks of long-term service in the future, witnessing the growth of Colum, meeting more challenges and opportunities together with the company, and becoming the backbone of promoting the development of the company.

"Twenty-eight years of riding the wind together, I grow up with Kelun", all the staff of Kelun-Biotech will be with good wishes for Kelun, and with the company to sail the waves together to make a new chapter!