LBA8 - Nivolumab (NIVO) + chemotherapy (chemo) vs chemo in patients (pts) with EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) with disease progression after EGFR tyrosine kinase inhibitors (TKIs) in CheckMate 722

Background

Treatment (tx) options are limited for pts with EGFR-mutated (mut) mNSCLC who experience disease progression following EGFR TKIs. CheckMate 722 (NCT02864251) is a randomized, open-label, phase 3 study of NIVO + chemo vs chemo in pts with EGFR-mut mNSCLC after progression on EGFR TKIs.

Methods

Pts with EGFR-mut mNSCLC (including uncommon mutations) with disease progression on 1 or 2 prior lines of EGFR TKI tx (including 1^st or 2^nd generation TKI for those with no T790M mutation and/or osimertinib regardless of T790M mutation) were stratified by tumor PD-L1, presence of brain metastases, smoking history, and prior osimertinib. Pts were randomized 1:1 to receive NIVO 360 mg Q3W + chemo (platinum + pemetrexed) Q3W or chemo for ≤ 4 cycles; pts without progression received NIVO + pemetrexed or pemetrexed, respectively, until disease progression, unacceptable toxicity or ≤ 2 y for NIVO. Primary endpoint: PFS. Secondary endpoints: OS, ORR, DOR, and 9- and 12-mo PFS rates.

Results

In all, 294 pts were randomized; baseline characteristics were well balanced between treatment arms. At final analysis (minimum follow-up: 18.2 mo), there was no statistically significant improvement in PFS with NIVO + chemo vs chemo (HR [95% CI]: 0.75 [0.56–1.00]; P = 0.053). No difference in PFS was seen between treatment arms across most subgroups except in pts with sensitizing EGFR mutations (n = 269) and 1 prior line of EGFR TKI tx (n = 248); HR (95% CI) was 0.72 (0.54–0.97) for both. Other efficacy results are presented (Table). Grade 3-4 treatment-related AEs occurred in 45% (NIVO + chemo) vs 29% (chemo) of pts. Table: LBA8

Efficacy outcomes with NIVO + chemo vs chemo

^aPer blinded independent central review.^bCalculated in pts with a response (NIVO + chemo, n = 45; chemo, n = 40).

Conclusions

NIVO + chemo did not show statistically significant improvement in PFS in pts with EGFR-mut mNSCLC after progression on EGFR TKIs; however, a trend of benefit was seen in pts with sensitizing EGFR mutations and in those with 1 prior line of EGFR TKI tx. No new safety signals were identified.

Clinical trial identification

NCT02864251.

Editorial acknowledgement

All authors contributed to and approved the abstract; writing and editorial assistance were provided by Thai Cao, MS, of Envision Pharma Group, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb (Princeton, NJ).

Funding

Bristol Myers Squibb (Princeton, NJ) and Ono Pharmaceutical Company Ltd. (Osaka, Japan).

Disclosure

T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi-Aventis, Takeda, PER, Daz Group, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Merck Pharmaceuticals HK Ltd, MiRXES, Novartis, OrigiMed Co. Ltd., Pfizer, Shanghai BeBirds Translation & Consulting Co., Ltd., Taiho Pharmaceutical Co., Ltd, AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science, Bayer Healthcare Pharmaceuticals Ltd., Covidien LP, C4 Therapeutics, Cirina Ltd., Da Volterrra, F. Hoffmann-La Roche Ltd / Genentech, Gilead Sciences, Lucence Health Inc., Medscape LLC / WebMD, MiRXES, OSE Immunotherapeutics, Pfizer, SFJ Pharmaceutical Ltd., Synergy Research, Tigermed, Vertex Pharmaceuticals, Berry Oncology, D3 Bio Ltd., Lakeshore Biotech; Financial Interests, Personal, Invited Speaker, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Officer, Chairman: ACT Genomics-Sanomics Group; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca; Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Personal, Advisory Role: geneDecode; Non-Financial Interests, Personal, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.; Non-Financial Interests, Personal, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non-Financial Interests, Personal, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Personal, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC). K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co.,Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, YODOSHA CO., LTD., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., TAIYO Pharma Co., Ltd.; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K.; Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Research Grant: PAREXEL International Corp., PRA HEALTHSCIENCES, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co.,Ltd., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services JAPAN K.K., SYNEOS HEALTH CLINICAL K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., SRL, Inc. K. Park: Financial Interests, Personal, Advisory Board: JNJ, Astra Zeneca, Daiichi Sankyo, BMS, Takeda; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Other, DMC member: BeiGene, Incyte; Financial Interests, Personal, Other, Advisor/Consultant: Genius, IMBdx; Financial Interests, Institutional, Research Grant: AstraZeneca, MSD. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, ONO, BMS, Eli Lilly, Boehringer Ingelheim, Takeda, MSD, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Celltrion, Amgen, Nippon Kayaku, Takeda, Pfizer, ONO, Janssen, AnHeart Therapeutics Inc; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Eli Lilly, Janssen, Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Takeda, ONO; Non-Financial Interests, Personal, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Personal, Member: ASCO. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). J.F. Gainor: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Genentech/Roche, Takeda, Lilly, Moderna, AstraZeneca, Pfizer, Novartis, iTeos, Karyopharm, Silverback Therapeutics, GlydeBio, BeiGene; Financial Interests, Personal, Stocks/Shares, Immediate family member is an employee. Note: Ironwood Pharmaceuticals is not involved in any oncology drug development. It is focused on gastroenterology.: Ironwood Pharmaceuticals; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Genentech, Bristol Myers Squibb, Merck, AstraZeneca, Moderna, Jounce, Alexo. X. Zhang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Sylvester: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S. Li: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J.C. Yang: Financial Interests, Institutional, Advisory Board: Astrazeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: Astrazeneca, Boehringer Ingelheim, Novartis, Astrazeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Personal, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Personal, Member: ASCO. All other authors have declared no conflicts of interest.