628MO - Comparing subcutaneous vs intravenous amivantamab with lazertinib in EGFR-mutated advanced NSCLC: Analysis of Asian patients from PALOMA-3

Background

PALOMA-3 (NCT05388669) showed that subcutaneous (SC) amivantamab plus lazertinib (ami+laz) had noninferior pharmacokinetics and objective response rate vs intravenous (IV) ami+laz in EGFR-mutated advanced non-small cell lung cancer (NSCLC) that progressed on osimertinib (osi) and chemotherapy. Overall survival (OS), a predefined exploratory endpoint, was longer for SC vs IV (HR, 0.62; 95% CI, 0.42-0.92; nominal P=0.02). SC administration required <5 min and had substantially reduced infusion-related reactions (IRRs) and venous thromboembolic events (VTE) vs IV. Here we evaluated efficacy and safety among Asian patients (pts) from PALOMA-3.

Methods

Pts with EGFR-mutated advanced NSCLC previously treated with osi and chemotherapy were randomized 1:1 to receive SC or IV ami+laz. Disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), OS, and safety among Asian pts are reported.

Results

Of 418 pts randomized, 255 were Asian (SC/IV, n=126/129). Median age was 61-62 y, 67% were female, and pts received a median of 2 prior lines of therapy. At a median follow-up of 6.9 mo, DCR was 80.2% (95% CI, 72.1-86.7%) for SC and 72.9% (95% CI, 64.3-80.3%) for IV (relative risk, 1.1 [95% CI, 0.96-1.27]). Median DoR was not estimable (NE) for SC vs 7.1 mo for IV. A favorable PFS trend was observed for SC vs IV (NE vs 5.6 mo; HR, 0.84; P=0.35). At 12 mo, 77% of pts were alive for SC vs 61% for IV; median OS was NE for both arms (HR, 0.60 [95% CI, 0.33-1.08]; P=0.08). Rate of IRRs was 6-fold lower for SC vs IV (10% vs 61%), mostly grade 1-2. For the first 4 mo of treatment, 74% of pts in the SC arm and 75% in the IV arm received prophylactic anticoagulants. VTE incidence was 11% for SC and 12% for IV among pts who received anticoagulants, vs 18% for SC and 22% for IV among pts who did not. Risk of clinically significant bleeding (grade ≥3) was low at 1% for pts on anticoagulants. Safety profile for Asian pts was consistent with the overall population.

Conclusions

Similar to the overall population, favorable trends were found for efficacy outcomes with SC vs IV ami+laz in Asian pts, with remarkably lower IRR and VTE rates with safe use of prophylactic anticoagulation.

Clinical trial identification

NCT05388669.

Editorial acknowledgement

Medical writing assistance was provided by David Le, PharmD (Lumanity Communications Inc).

Legal entity responsible for the study

Janssen Pharmaceuticals.

Funding

Janssen Pharmaceuticals.

Disclosure

S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Pfizer, Eli Lilly, BMS/Ono, Takeda, Janssen, IMBdx, Merck (German), Novartis, Abion, Abion, Beigene, ImmuneOncia, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck Sharp & Dohme, Eli Lilly, Amgen, Yuhan; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZeneca, Lunit. H. Akamatsu: Financial Interests, Personal, Advisory Board: Amgen Inc, Janssen Pharmaceutical K.K., Sandoz; Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Nippon Kayaku. Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer Inc, Takeda Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Coordinating PI: Amgen Inc, Chugai Pharmaceutical Co. Ltd. J.C. Yang: Financial Interests, Institutional, Advisory Board: AbbVie, Amgen, AnHeart Therpeutics, ArriVent, AstraZeneca, Bayer, Black Diamond Therapeutics Inc., Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GSK, Gilead, Janssen, MSD, Merck KGaA, Novartis, Ono Pharmaceuticals, Pfizer, Regeneron, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis; Financial Interests, Personal and Institutional, Coordinating PI, Travel to major meeting to present the trial results: AstraZeneca, Dizal Pharmaceutical; Financial Interests, Personal and Institutional, Coordinating PI, Travel to major meeting to present the trial result: Merck Sharp & Dohme Corporation; Financial Interests, Personal, Steering Committee Member: Numab Therapeutics AG, Merck KGaA, Ipsen, Takeda Oncology, Daiichi Sankyo, Eli Lilly, Janssen Pharmaceuticals, ArriVent, Amgen, Bayer, Yuhan Pharmaceuticals, Black Diamond Therapeutics Inc.; Non-Financial Interests, Personal, Member: IASLC, ASCO. S.M. Lim: Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Roche, GSK, Jiansu Hengrui, Amgen, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: BridgeBio Therapeutics, Oscotec. T. John: Financial Interests, Personal, Invited Speaker, Speaker tour Vietnam: AstraZeneca; Financial Interests, Personal, Invited Speaker, CTIO: Merck Sharp Dohme; Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Bayer, Specialised Therapeutics; Financial Interests, Institutional, Advisory Board: Roche, Novartis, Pfizer, Amgen, Takeda, PharmaMar, Johnson and Johnson, Seagen Pharmaceuticals, Merck Serono; Non-Financial Interests, Personal, Principal Investigator, Oceanic study: AstraZeneca. Y. Ohe: Financial Interests, Personal, Advisory Board: Amgen, AnHeart Therapeutics Inc, AstraZeneca, BMS, Celltrion, Nippon Kayaku, ONO, Pfizer, Takeda, PharmaMar, AnHeart; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, MSD, Novartis, ONO, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Janssen, Amgen; Financial Interests, Personal and Institutional, Coordinating PI: Takeda, ONO; Non-Financial Interests, Personal, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Personal, Member: ASCO. M. Kondo: Financial Interests, Personal, Local PI: Janssen. M. Tamiya: Financial Interests, Institutional, Local PI: Janssen; Financial Interests, Personal, Advisory Board: Pfizer, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: AstraZeneca, Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly; Financial Interests, Personal and Institutional, Local PI: Daiichi Sankyo, MSD. P. Danchaivijitr: Financial Interests, Personal, Advisory Role, Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board, Invited Speaker: AstraZeneca. J. Zhuo, C. Saadoun, G. Balaburski: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson. N. Saxena L. Ribeiro, M. Gamil, M. Baig: Financial Interests, Personal, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Other, Stocks: Johnson and Johnson. All other authors have declared no conflicts of interest.