389P - Updated efficacy and safety of pralsetinib in Chinese patients with advanced RET fusion+ non-small cell lung cancer

Background

Pralsetinib is a potent, selective Rearranged during Transfection (RET) inhibitor targeting oncogenic RET alterations and is the first RET inhibitor approved in China. ARROW is a global phase I/II registrational study to evaluate the safety and efficacy of pralsetinib in a variety of advanced RET altered solid tumors including non-small cell lung cancer (NSCLC). Here we present updated results of the ARROW study in Chinese patients with advanced RET fusion+ NSCLC.

Methods

RET fusion+ Chinese NSCLC patients with or without prior platinum-based chemotherapy were enrolled and administered with pralsetinib 400 mg QD. The primary endpoints were objective response rate (ORR) by blinded independent central review per RECIST v1.1 and safety.

Results

As of 4 Mar 2022, 68 Chinese patients with RET fusion+ NSCLC received pralsetinib. Amongst 37 patients who were previously treated with platinum-based chemotherapy, ORR was 66.7% (22/33; 95% CI 48-82; 1 CR, 21 PR) in 33 patients with measurable lesions at baseline; median PFS (95% CI) was 11.7 months (8.7; -) and 24-month PFS rate was 37.5%. Amongst 31 patients who were treatment-naïve, ORR was 83.3% (25/30, 95% CI 65-94; 2 CR, 23 PR) in 30 patients with measurable lesions at baseline; median PFS (95% CI) was 12.7 months (8.9; -) and 18-month PFS rate was 36.2%. The most frequently reported treatment-related adverse events (TRAEs) in all (N=68) NSCLC patients were aspartate aminotransferase increased (82%), neutrophil count decreased (79%), anaemia (72%), white blood cell count decreased (62%), and alanine aminotransferase increased (57%). 11.8% of patients discontinued pralsetinib due to TRAEs.

Conclusions

With longer follow-up, pralsetinib continues to demonstrate deep and durable response and long-term clinical benefit in RET fusion+ NSCLC Chinese patients with or without prior platinum-based chemotherapy. Updated results are consistent with previously reported results from the global population in the ARROW trial. Pralsetinib in Chinese patients has a manageable safety profile, with no new safety signals detected. Overall, pralsetinib showed a favorable benefit-risk profile, offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

Clinical trial identification

NCT03037385.

Editorial acknowledgement

Medical writing and editorial support were provided by Mengxin Chen, and were funded by CStone Pharmaceuticals (Suzhou) Co., Ltd.

Legal entity responsible for the study

CStone Pharmaceuticals (Suzhou) Co., Ltd.

Funding

CStone Pharmaceuticals (Suzhou) Co., Ltd.

Disclosure

Q. Zhou: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lily, MSD, Pfizer, Roche, Sanofi. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, Beigen, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, BMS. M. Qin, Z. Shen, S. Yao:Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (SuZhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (SuZhou) Co., Ltd. X. Duan: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (SuZhou) Co., Ltd. J. Yang: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (SuZhou) Co., Ltd.; Financial Interests, Personal, Leadership Role: CStone Pharmaceuticals (SuZhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (SuZhou) Co., Ltd. All other authors have declared no conflicts of interest.