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Displaying One Session

Mini Oral session
Date
Sun, 19.09.2021
Time
17:30 - 18:30
Location
Channel 1
Mini Oral session

LBA49 - Efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) and actionable genomic alterations (AGAs): Preliminary results from the phase I TROPION-PanTumor01 study

Presentation Number
LBA49
Speakers
  • Edward B. Garon (Santa Monica, CA, United States of America)
Lecture Time
17:30 - 17:35
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30

Abstract

Background

Pts with adv/met NSCLC with AGAs derive limited benefit from existing treatments once tyrosine kinase inhibitors (TKIs) and platinum chemotherapies fail. Dato-DXd is an antibody-drug conjugate comprising a TROP2-directed monoclonal antibody conjugated to a potent topoisomerase I inhibitor via a stable tetrapeptide-based cleavable linker. Dato-DXd showed encouraging antitumor activity in the phase 1 TROPION-PanTumor01 trial in heavily pretreated pts with adv/met NSCLC treated with 4, 6, and 8 mg/kg. Here, we report results from this trial for pts with NSCLC with AGAs.

Methods

TROPION-PanTumor01 (NCT03401385) is an ongoing multicenter, open-label, dose-expansion study evaluating Dato-DXd in solid tumors, including NSCLC in 210 pts. It is assessing safety, pharmacokinetics, antitumor activity, and biomarkers in pts who progressed after standard treatment or had no standard treatment available and had measurable disease. Stable/treated brain metastases were permitted. Pts were not selected based on TROP2 expression or AGA status.

Results

34 pts had adv/met NSCLC with AGAs (8 at 4 mg/kg, 10 at 6 mg/kg, and 16 at 8 mg/kg). Median age was 62 years; 56% were women and 44% were men. Investigator-reported AGAs were EGFR (n=29), ALK (n=3), and ROS1 and RET (both n=1). 82% of pts received ≥3 prior regimens and 85% prior TKI; 69% of pts with EGFR mutations had prior osimertinib. Median duration on study was 13 months. Confirmed ORR by BICR across doses was 35% (95% CI, 19.7-53.5). Median DOR was 9.5 months (95% CI, 3.3-NE). Most common any-grade AEs were nausea (62%) and stomatitis (56%); hematologic toxicities were infrequent. There was 1 incidence of treatment-related adjudicated interstitial lung disease, a grade 5 event at 8 mg/kg.

Conclusions

Antitumor activity and safety in adv/met NSCLC pts with AGAs are encouraging. The ongoing phase 2 TROPION-Lung05 trial (NCT04484142) is assessing Dato-DXd at 6 mg/kg in adv/met NSCLC with AGAs after targeted therapies and platinum chemotherapy.

Clinical trial identification

NCT03401385.

Editorial acknowledgement

Medical writing support was provided by Christine Zink, MD, of SciMentum, Inc, a Nucleus Holdings Ltd company, and was funded by Daiichi Sankyo, Inc. Editorial support was provided in accordance with Good Publication Practice guidelines.

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

E.B. Garon: Financial Interests, Personal, Advisory Role: ABL Bio; Boehringer Ingelheim; Bristol Myers Squibb; Dracen; Eisai; EMD Serono; GlaxoSmithKline; Merck; Novartis; Sanofi; Shionogi; Xilio Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Bristol Myers Squibb; Dynavax Technologies; EMD Serono; Genentech; Iovance Biotherapeutics; Lilly; Merck; Mirati Therapeutics; Neon Therapeutics; Novartis. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, Boehringer Ingelheim, Calithera, Checkpoint Therapeutics, Corvus, Curis, CytomX, Daiichi Sankyo, Dracen, Dynavax, Lilly, EMD Se; Financial Interests, Institutional, Advisory Role: AbbVie, Achilles Therapeutics, Amgen, AstraZeneca, Atreca, Boehringer Ingelheim, Bristol Myers Squibb, Calithera, Checkpoint Therapeutics, Daiichi Sankyo, Editas Medicine, Eisai, EMD Serono, G1 Therapeutics, Genentech/Roche, GlaxoSmithKline, Gritstone Onc; Financial Interests, Personal, Other, Consulting- Spouse: Astellas and Otsuka Pharmaceuticals. A.E. Lisberg: Financial Interests, Personal, Other, Employment (Immediate Family Member): Boston Scientific; Financial Interests, Personal, Stocks/Shares: Boston Scientific; Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca, Bristol Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals, WindMIL. A. Spira: Financial Interests, Personal, Stocks/Shares, Stock and Other Ownership Interests: Lilly; Financial Interests, Personal, Invited Speaker, Honoraria: Amgen; AstraZeneca/MedImmune; Bayer; Bristol Myers Squibb; CytomX Therapeutics; Janssen Oncology; Merck; Novartis; Takeda; Financial Interests, Institutional, Advisory Role: Amgen; Array BioPharma; AstraZeneca/MedImmune; Bristol Myers Squibb; Merck; Financial Interests, Personal, Advisory Role: Gritstone Oncology; Incyte; Jazz Pharmaceuticals; Mirati Therapeutics; Novartis; Financial Interests, Institutional, Research Grant: AbbVie; ADC Therapeutics; ADC Therapeutics; Amgen; Arch Therapeutics; Astellas Pharma; Astex Pharmaceuticals; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; CytomX Therapeutics; Daiichi Sankyo; Gritstone Oncology; Ignyta; Incyte; Janssen Oncolog. N. Yamamoto: Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca; Chugai Pharma; Daiichi Sankyo/UCB Japan; Lilly Japan; Ono Pharmaceutical; Pfizer; Sysmex; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Chugai Pharma; CMIC; Eisai; Otsuka; Takeda; Financial Interests, Institutional, Advisory Role: AbbVie; Astellas Pharma; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Chugai Pharma; Daiichi Sankyo; Eisai; GlaxoSmithKline; Janssen; Kyowa Hakko Kirin; Lilly Japan; Merck Serono; MSD; Novartis; Ono Pharmaceutical; Pfizer; Sumitomo Dainippon; Taiho; Financial Interests, Personal, Advisory Role: Chiome Bioscience; Otsuka. R.S. Heist: Financial Interests, Personal, Invited Speaker, Honoraria: Chugai/Roche; Financial Interests, Personal, Advisory Role: Apollomics; Boehringer Ingelheim; Daichii Sankyo; Daichii Sankyo; EMD Serono/Merck; EMD Serono/Merck; Novartis; Tarveda Therapeutic; Financial Interests, Institutional, Research Grant: AbbVie; Agios; Celgene; Corvus Pharmaceuticals; Daiichi Sankyo; Debiopharm Group; Exelixis; Incyte; Lilly; Millennium; Mirati Therapeutics; Novartis; Peregrine Pharmaceuticals; Pfizer; Roche; Turning Point Therapeutics. J.M. Sands: Financial Interests, Personal, Advisory Role: AstraZeneca; AstraZeneca; Blueprint Medicines; Boehringer Ingelheim; Daiichi Sankyo/UCB Japan; Foundation Medicine; Guardant Health; Jazz Pharmaceuticals; Lilly; Medtronic; Medtronic; PharmaMar; Takeda Travel, Accommodations, Expenses - AstraZeneca. K. Yoh: Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb Japan; Chugai Pharma; Janssen; Kirin Pharmaceuticals; Lilly Japan; Novartis; Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Chugai Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca; Bayer; Bristol Myers Squibb; Chugai Pharma; Daiichi Sankyo; Lilly Japan; MSD; Novartis; Ono Pharmaceutical; Pfizer; Taiho Pharmaceutical; Takeda. F. Meric-Bernstam: Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Personal, Invited Speaker, Honoraria: Mayo Clinic; Rutgers Cancer Institute of New Jersey; Financial Interests, Personal, Advisory Role: Aduro Biotech; Alkermes; Debiopharm Group; eFFECTOR Therapeutics; Genentech; IBM Watson Health; Immunomedics; Inflection Biosciences; Jackson Laboratory for Genomic Medicine; Kolon Life Sciences; Mersana; Origimed; PACT Pharma; Parexel International; Pfiz; Financial Interests, Institutional, Research Grant: AbbVie; Aileron Therapeutics; AstraZeneca; Bayer;; Calithera Biosciences; Curis; CytomX Therapeutics; Daiichi Sankyo; Debiopharm Group; eFFECTOR Therapeutics; Genentech; GlaxoSmithKline; Guardant Health; Jounce Therapeutics; Millennium; Novartis; Pfizer; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Beth Israel Deaconess Medical Center; Taiho Pharmaceutical. J. Greenberg: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. F. Kobayashi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Kawasaki: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Co., LTD. L. Jukofsky: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. K. Nakamura: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. T. Shimizu: Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis, AbbVie, Daiichi Sankyo, Takeda Oncology, Eli Lilly, Loxo Oncology, Bristol Myers Squibb, Eisai, Pfizer, AstraZeneca, Incyte, Symbio Pharmaceuticals, Chordia Therapeutics, 3D-Medicine, Five Prime, PharmaMar, Astellas; Financial Interests, Personal, Invited Speaker, Honoraria: Daiichi Sankyo, AbbVie, Taiho, Eisai, MSD, Takeda Oncology, Amgen; Financial Interests, Personal, Other, Support for attending meetings and travel: The Consortium on Harmonization of Institutional Requirements for Clinical Research (CHAIR) Joint Scientific Committee Review Member and External IRB Member of Phase 1 Trials in Hong Kong, HKSAR, China. All other authors have declared no conflicts of interest.

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Mini Oral session

1192MO - Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: Analysis from the CHRYSALIS study

Presentation Number
1192MO
Speakers
  • Natasha B. Leighl (Toronto, ON, Canada)
Lecture Time
17:35 - 17:40
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30

Abstract

Background

Amivantamab (ami), an epidermal growth factor receptor (EGFR)-MET bispecific antibody, has demonstrated efficacy in EGFR mutant non-small cell lung cancer (NSCLC) that progressed on osimertinib (osi), both as monotherapy and in combination with lazertinib (laz), a 3rd-generation tyrosine kinase inhibitor. Clinical outcomes of patients (pts) treated with ami monotherapy (mono) and ami in combination with laz (combo) are presented here.

Methods

CHRYSALIS is an ongoing study of ami in pts with advanced EGFR mutant NSCLC (NCT02609776). Pts who progressed on osi were pooled to form the mono group, a majority of whom were preselected for C797S/other resistance mutations or MET amplification. The combo group comprised unselected pts who had progressed on osi but were chemotherapy-naïve. Response was assessed by the investigator per RECIST v1.1.

Results

As of 19 Apr 2021, 121 pts in the mono group (85% with EGFR/MET-based resistance) and 45 in the combo group (38% with EGFR/MET-based resistance) were efficacy-evaluable, with median follow-up of 6.9 and 11.1 months, respectively. Antitumor activity was observed in the mono group, with 33 achieving partial response (PR) as best response, of which 23 were confirmed, for an overall response rate (ORR) of 19% (95% CI, 12–27). In the combo group, 1 complete response and 15 PRs were observed, all of which confirmed, for an ORR of 36% (95% CI, 22–51). Median duration of response was 5.9 months with mono, 9.6 months with combo (Table). The safety profile for both mono and combo was consistent with previously-reported safety. No new safety signals were identified.

Conclusions

Antitumor activity of ami + laz in the post-osi setting appears favorable even without molecular selection post osimertinib failure, supporting that simultaneous targeting of the extracellular and catalytic domains of EGFR provides additive benefits.

Efficacy of amivantamab monotherapy and in combination with lazertinib among efficacy-evaluablea patients

Efficacy
Monotherapy (n=121) Combination (n=45)
ORR (95% CI) 19% (12–27) 36% (22–51)
CBR (95% CI) 48% (39–57) 64% (49–78)
mDOR, month (95% CI) 5.9 (4.2–12.6) 9.6 (5.3–NR)

aPatients who had at least 2 post-baseline disease assessment or discontinued before the second assessment. CBR, clinical benefit rate (complete response, partial response, or stable disease of at least 11 weeks); mDOR, median duration of response; ORR, overall response rate; NR, not reached

Clinical trial identification

NCT02609776.

Editorial acknowledgement

Medical writing assistance was funded by Janssen Global Services, LLC. and provided by Tracy T. Cao, PhD (Janssen Global Services, LLC.).

Legal entity responsible for the study

Janssen.

Funding

Janssen.

Disclosure

N.B. Leighl: Financial Interests, Personal, Advisory Role: Xcovery; Financial Interests, Personal, Other, travel, accommodations, expenses: Merck Sharp & Dohme, Bristol Myers Squibb, Nektar, GlaxoSmithKline, Roche, AstraZeneca; Financial Interests, Personal, Other, honoraria: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Novartis, Roche Canada, Guardant Health, MSD, EMD Serono, Lilly. C.A. Shu: Financial Interests, Personal, Advisory Board: Genentech, AstraZeneca, Janssen, Mirati. A. Minchom: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceuticals, Novartis Oncology, Bayer Pharmaceuticals; Financial Interests, Personal, Advisory Board: Janssen Pharmaceuticals, Merck Pharmaceuticals; Financial Interests, Personal, Other: Amgen Pharmaceuticals, Loxo Oncology; Financial Interests, Personal, Advisory Role: Faron Pharmaceuticals. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Medical Trends, Merck Sharp & Dohme, Merck Serono, Peptomyc, Pfizer, Puma, Regeneron, Sanofi, Syneos Health, Take; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Peervoice, Pfizer, Springer, Touch Medical; Financial Interests, Personal, Member of the Board of Directors: Grífols. B.C. Cho: Financial Interests, Personal and Institutional, Research Grant: Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Non-Financial Interests, Personal, Other: DAAN Biotherapeutics. K. Park: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, Loxo, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, Johnson & Johnson, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim, AZD; Financial Interests, Personal, Funding: AstraZeneca, MSD Oncology. J. Han: Financial Interests, Personal, Advisory Role: MSD Oncology, AstraZeneca, Bristol Myers Squibb, Lilly, Novartis, Takeda, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Bristol Myers Squibb, Takeda; Financial Interests, Personal, Funding: Roche, Pfizer, Ono Pharmaceutical, Takeda. M. Boyer: Financial Interests, Personal, Invited Speaker: Merck Sharpe & Dohme, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Merck Sharpe & Dohme, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Roche, Merck Sharpe & Dohme, AstraZeneca, Amgen, Pfizer, Novartis, Bristol Myers Squibb, ImmuGene, Merck KGaA, Lilly, Janssen; Non-Financial Interests, Institutional, Principal Investigator: Roche, Merck Sharpe & Dohme, AstraZeneca, Amgen, Pfizer, Novartis, Bristol Myers Squibb, ImmuGene, Merck KGaA, Lilly, Janssen. C.K. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Pfizer, GSK, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca. V. Moreno Garcia: Non-Financial Interests, Institutional, Principal Investigator: AbbVie, Acea Bio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, Beigen, BioInvent International AB, BMS, Boehringer Ingelheim, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Therapeutics, Exelixis, Forma Therapeutics; Financial Interests, Personal, Advisory Role: Roche, Bayer, Pieris, BMS, Janssen, Basilea; Financial Interests, Personal, Other, Travel: Regeneron/Sanofi, BMS, Bayer; Financial Interests, Personal, Speaker’s Bureau: Nanobiotix, BMS, Bayer; Financial Interests, Personal, Other, Educational Grant: Medscape/Bayer. P. Tomasini: Financial Interests, Personal, Invited Speaker: AZ, Roche, BMS, Takeda, BI; Non-Financial Interests, Personal, Invited Speaker: AZ, Roche, BMS, Takeda, BI; Financial Interests, Personal, Expert Testimony: AZ, Roche, BMS, Takeda, BI; Non-Financial Interests, Personal, Expert Testimony: AZ, Roche, BMS, Takeda, BI; Non-Financial Interests, Institutional, Principal Investigator: AZ, Roche, BMS, Takeda, Amgen, Johnson & Johnson. S. Viteri: Financial Interests, Personal, Advisory Role: Roche, Bristol Myers Squibb, Janssen; Financial Interests, Personal, Speaker’s Bureau: Roche, Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Other, travel, accommodations, expenses: MSD. J. Xie: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Mertz: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. E. Artis: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.W. Schnepp: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Thayu: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J.M. Trigo Perez: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Takeda; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Other, Travel grant: MSD; Financial Interests, Institutional, Research Grant: BMS; Non-Financial Interests, Personal, Advisory Role: BMS; Non-Financial Interests, Personal, Advisory Role: Merck. All other authors have declared no conflicts of interest.

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Mini Oral session

1193MO - Amivantamab plus lazertinib in post-osimertinib, post-platinum chemotherapy EGFR-mutant non-small cell lung cancer (NSCLC): Preliminary results from CHRYSALIS-2

Presentation Number
1193MO
Speakers
  • Catherine A. Shu (New York, NY, United States of America)
Lecture Time
17:40 - 17:45
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30

Abstract

Background

The combination of amivantamab (ami), an epidermal growth factor receptor (EGFR)-MET bispecific antibody, with the 3rd-generation tyrosine kinase inhibitor lazertinib (laz), yielded a 36% overall response rate (ORR) in the post-osimertinib (osi), chemotherapy-naïve setting (Cho Ann Oncol 2020;31:S813, Oral 1258). The activity of ami + laz after progression on both osi and platinum doublet chemotherapy is unknown.

Methods

CHRYSALIS-2 (NCT04077463) is an ongoing open-label study that includes a single-arm cohort (Cohort A) examining ami + laz in patients (pts) with EGFR Exon19del or L858R NSCLC whose disease progressed after standard of care osi and platinum chemotherapy (3rd / 4th line; “target” population) and in more heavily-pretreated (5th line +) pts. Pts received the established recommended combination dose of 1050 mg IV ami (1400 mg, ≥80 kg) + 240 mg oral laz. Investigator-assessed response per RECIST v1.1 is reported for pts with ≥2 post-baseline disease assessments.

Results

As of 19 Apr 2021, 116 pts were enrolled in Cohort A (median 63 y, 68% women, 60% Asian, median of 3 [range, 2–14] prior lines), with 59 in the target and 57 in the heavily-pretreated populations. Of 28 response-evaluable pts in the target population, 12 (43% [95% CI, 24–63]) reported partial response (PR) as best response; of the 12 responses, 9 were confirmed (3 pending), for an overall response rate (ORR) of 32% (95% CI, 16–52). Of 45 pts in the heavily-pretreated population, 7 reported best response of PR, of which 6 were confirmed (1 pending), for an ORR of 13% (95% CI, 5–27). At 3.7-mo median follow-up, 17 pts in the target population remain on treatment: 10 with PR (3 pending confirmation) and 7 with stable disease. The safety profile for Cohort A was consistent with previously reported experience with ami + laz at the recommended combination dose, and no new safety signals were identified.

Conclusions

Ami + laz is showing encouraging early activity in a population that progressed on both standard of care osi and platinum chemotherapy. Activity is consistent with the post-osi population, suggesting intervening chemotherapy does not impact ami + laz activity.

Clinical trial identification

NCT04077463.

Editorial acknowledgement

Medical writing assistance was funded by Janssen Global Services, LLC. and provided by Tracy T. Cao, PhD (Janssen Global Services, LLC.).

Legal entity responsible for the study

Janssen.

Funding

Janssen.

Disclosure

C.A. Shu: Financial Interests, Personal, Advisory Board: Genentech, AstraZeneca, Janssen, Mirati. K. Goto: Financial Interests, Personal, Invited Speaker: Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K. Y. Ohe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin; Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Ono, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku; Financial Interests, Personal, Research Grant: AstraZeneca, Chugai, Lilly, Ono, BMS, Kyorin, Dainippon Sumitomo, Pfizer, Taiho, Novartis, Ignyta, Takeda, Kissei, Daiichi Sankyo, Janssen, Loxo. B. Besse: Financial Interests, Institutional, Research Grant: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE Immunotherapeutics, Pfizer, Roche-Genentech. K. Park: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, Loxo, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, Johnson & Johnson, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim, AZD; Financial Interests, Personal, Funding: AstraZeneca, MSD Oncology. F. Griesinger: Financial Interests, Personal, Other, honoraria: Roche/Genentech, Boehringer Ingelheim, Pfizer, AbbVie. MSD, Bristol Myers Squibb, Ipsen, Novartis, AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche/Genentech, Pfizer, Boehringer Ingelheim, MSD, Bristol Myers Squibb, Celgene, Takeda, AbbVie, Novartis, Bayer, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Celgene, Lilly, Novartis, Pfizer, Roche, Takeda. J.C. Yang: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Novartis, AstraZeneca, Roche/Genentech, Clovis Oncology, Lilly, MSD Oncology, Merck Serono, Celgene, Astellas Pharma, Bayer, Pfizer, Ono Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim, AstraZeneca, Yuhan, Hansoh, Blueprint; Financial Interests, Personal, Other, travel, accommodation, expenses: Pfizer; Financial Interests, Personal, Other, honoraria: Boehringer Ingelheim, Roche, MSD, AstraZeneca, Novartis, Bristol Myers Squibb, Ono Pharmaceuticals, Takeda, Lilly, Pfizer. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Medical Trends, Merck Sharp & Dohme, Merck Serono, Peptomyc, Pfizer, Puma, Regeneron, Sanofi, Syneos Health, Take; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Peervoice, Pfizer, Springer, Touch Medical; Financial Interests, Personal, Member of the Board of Directors: Grífols. R.E. Sanborn: Financial Interests, Personal, Advisory Role: Genentech/Roche, AstraZeneca, EMD Serono, Blueprint Medicines, Daiichi Sankyo/Lilly, Janssen Oncology; Financial Interests, Personal, Other, travel, accommodation, expenses: AstraZeneca; Financial Interests, Personal, Other, honoraria: AstraZeneca, Amgen; Financial Interests, Institutional, Funding: Bristol Myers Squibb, MedImmune; Financial Interests, Personal, Funding: Merck, AstraZeneca. R. Bernabe Caro: Financial Interests, Personal, Invited Speaker: Roche, Astra, BMS, Pfizer; Financial Interests, Personal, Advisory Board: Astra, BMS, Roche; Financial Interests, Personal, Research Grant: Roche. J.M. Bauml: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck, AstraZeneca, Genentech, Celgene, Boehringer Ingelheim, Guardant Health, Takeda, Novartis, Janssen, Ayala Pharmaceuticals, Regeneron, Inivata, Novartis, Foundation Medicine; Financial Interests, Institutional, Funding: Merck, Carevive Systems, Novartis, Incyte, Bayer, Janssen, AstraZeneca, Takeda, Amgen, Pfizer, Mirati Therapeutics. J. Chen: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson. E. Fennema: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Mahoney: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. L. Trani: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Thayu: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. B.C. Cho: Financial Interests, Personal and Institutional, Research Grant: Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Non-Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. All other authors have declared no conflicts of interest.

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Mini Oral session

Discussion LBA49, 1192MO and 1193MO

Speakers
  • Sai-Hong I. Ou (Orange, CA, United States of America)
Lecture Time
17:45 - 18:00
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30
Mini Oral session

LBA50 - A randomized phase III study comparing cisplatin-pemetrexed (cis-pem) with carboplatin (C)-paclitaxel (P)-bevacizumab (B) in chemotherapy naïve patients (pts) with advanced KRAS mutated non-small cell lung cancer (NSCLC): NVALT22

Presentation Number
LBA50
Speakers
  • Anne-Marie C. Dingemans (Rotterdam, Netherlands)
Lecture Time
18:00 - 18:05
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30

Abstract

Background

We previously showed in a retrospective multi-center analysis in pts with KRAS mutated NSCLC that outcome with first-line platinum-based chemotherapy was improved with taxane-based combinations compared to other regimens (Mellema, Lung Cancer 2015; 90:245). Therefore, we initiated NVALT22, a multi-center open-label randomized phase III study comparing cis-pem and CPB in pts with advanced KRAS mutated NSCLC. Here we present the progression free survival (PFS) as assessed by local investigator.

Methods

Pts with stage IIIB/ IV KRAS mutated NSCLC were randomized 1:1 to up to 6 cycles of C (AUC6), P (200 mg/m2), and B (15 mg/kg), every 3 weeks (Q3W), followed by B maintenance; or cis (75 mg/m2) and pem (500 mg/m2), Q3W, followed by pem maintenance. Stratification factors: KRAS mutation (G12C/G12V/other), performance status (ECOG 0-1/2), brain metastases (y/n). In 2018 the study was amended: prior pembrolizumab was allowed and added as stratification factor (y/n). Response assessment was performed every 6 weeks (RECIST 1.1). Primary endpoint: PFS. Secondary endpoints: overall response rate, disease control rate and overall survival. The trial was designed to demonstrate superiority of CPB over cis-pem, assumed hazard ratio (HR) 0.67. 201 events and a total sample size of 240 pts were required.

Results

Inclusion was closed prematurely due to slow accrual, mainly due to change of first-line treatment landscape. 203 pts (53% female, median age 65 (range 59 – 70), 45% G12C mutation, 95% ECOG ≤1, 13% history of brain metastasis, 13% prior pembrolizumab) were randomized. At data cutoff (August 16, 2021) median follow-up was 38.3 mo (95% confidence interval (CI) 33.5 – 47.6) and 184 events occurred. Median (95% CI) PFS was 5.2 mo (4.4 – 6.2) for CPB vs 4.7 mo (3.9 – 5.9) for cis-pem, HR 0.96 (95% CI 0.70 – 1.31), p = 0.81. In pts with a G12C mutation CPB showed a HR of 0.74 (95% CI 0.47 – 1.16), p = 0.22.

Conclusions

CPB did not improve PFS compared to cis-pem in pts with advanced KRAS mutated NSCLC.

Clinical trial identification

NCT02743923 (April 19th, 2016); EudraCT 2015-003121-34.

Legal entity responsible for the study

Stichting NVALT studies.

Funding

Eli Lilly; Roche.

Disclosure

A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Amgen; Non-Financial Interests, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Member: IASCL; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR. S. Burgers: Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim. L.E.L. Hendriks: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Takeda; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche. T.J.N. Hiltermann: Financial Interests, Institutional, Advisory Board: AZD; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BSM; Financial Interests, Institutional, Research Grant: Roche. E.F.F. Smit: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: cellgene; Financial Interests, Institutional, Advisory Board: dsi; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Takeda; Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche. J.A. De Langen: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: bms; Financial Interests, Institutional, Advisory Board: boehringer ingelheim; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: MSD. All other authors have declared no conflicts of interest.

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Mini Oral session

LBA51 - EMPOWER-Lung 3: Cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC)

Presentation Number
LBA51
Speakers
  • Miranda Gogishvili (Tbilisi, Georgia)
Lecture Time
18:05 - 18:10
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30

Abstract

Background

EMPOWER-Lung 3 is a randomised, 2-part, Phase 3 study of 1L treatment of patients (pts) with advanced (Stage III/IV) squamous (SQ) or non-squamous (NSQ) NSCLC without actionable mutations (NCT03409614). The double-blind Part 2 of the study enrolled pts irrespective of PD-L1 levels and compared clinical activity and safety of cemiplimab, an anti -PD-1, plus (+) platinum-based chemo, versus (vs) placebo (PBO)+chemo.

Methods

Pts were randomised (2:1; stratified by histology and PD-L1 expression) to receive cemiplimab 350 mg once every 3 weeks (Q3W) or PBO Q3W for 108 weeks (or until progression), plus up to 4 cycles of chemo (followed by mandatory pemetrexed maintenance for NSQ pts assigned to a pemetrexed-containing regimen). Primary endpoint was overall survival (OS). Key secondary endpoints include progression-free survival (PFS) and objective response rate (ORR) per blinded independent central review. Here we report Part 2 results from the pre-specified 2nd interim analysis. Data cut-off was 14 June 2021.

Results

Overall, 466 pts were eligible and randomised to cemiplimab+chemo (n=312) or PBO+chemo (n=154). Median (range) age was 63.0 (25-84) years; 57.1% had NSQ NSCLC; and 85.2% had Stage IV disease. Median OS was 21.9 months with cemiplimab+chemo vs 13.0 months with PBO+chemo (HR, 0.71; P=0.014). Cemiplimab+chemo was associated with superior median PFS (8.2 vs 5.0 months; HR, 0.56), higher ORR (43.3% vs 22.7%), and longer median duration of response (DOR) (15.6 months vs 7.3 months) vs PBO+chemo (Table). Incidence of Grade ≥3 adverse events was 43.6% in cemiplimab+chemo arm and 31.4% in PBO+chemo arm.

Cemiplimab+chemo (n=312) PBO+chemo (n=154)
Duration of follow-up, median (IQR), months 16.3 (13.9–19.1) 16.7 (14.2–19.0)
OS, median (95% CI), months 21.9 (15.5–NE) 13.0 (11.9–16.1)
HR (95% CI) 0.71 (0.53–0.93); P=0.014
PFS, median (95% CI), months 8.2 (6.4–9.3) 5.0 (4.3–6.2)
HR (95% CI) 0.56 (0.44–0.70); P<0.0001
ORR, % (95% CI) 43.3 (37.7–49.0) 22.7 (16.4–30.2)
Odds ratio (95% CI) 2.68 (1.72–4.19); P<0.0001
Complete response, n (%) 8 (2.6) 0 (0)
Partial response, n (%) 127 (40.7) 35 (22.7)
Kaplan-Meier estimated DOR, median (95% CI), months 15.6 (12.4–NE) 7.3 (4.3–12.6)

Conclusions

In pts with advanced NSCLC, 1L cemiplimab+chemo demonstrated clinically meaningful and statistically significant improvement in OS, PFS, ORR and DOR vs chemo alone, with a safety profile consistent with cemiplimab monotherapy and platinum-based chemo.

Clinical trial identification

NCT03409614.

Editorial acknowledgement

Medical writing support was provided by Jenna Lee, MS, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc., and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc., and Sanofi.

Disclosure

K.D. Penkov: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Advisory Role: Roche. E. Kalinka: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals. C. Gessner: Financial Interests, Personal, Other, Advisory board fees or honoraria: GlaxoSmithKline; Financial Interests, Personal, Other, Advisory board fees or honoraria: Pfizer; Financial Interests, Personal, Other, Advisory board fees or honoraria: AstraZeneca; Financial Interests, Personal, Other, Advisory board fees or honoraria: Roche; Financial Interests, Personal, Other, Advisory board fees or honoraria: Novartis; Financial Interests, Personal, Other, Advisory board fees or honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Advisory board fees or honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Advisory board fees or honoraria: Berlin-Chemie; Financial Interests, Personal, Other, Advisory board fees or honoraria: Chiesi; Financial Interests, Personal, Other, Advisory board fees or honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Advisory board fees or honoraria: Sanofi. R. Passalacqua: Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sanofi-Aventis; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Pierre-Fabre. S. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. K. McGuire: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. R.G.W. Quek: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.

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Mini Oral session

1194MO - Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results

Presentation Number
1194MO
Speakers
  • Luis Paz-Ares (Madrid, Spain)
Lecture Time
18:10 - 18:15
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30

Abstract

Background

In patients (pts) with advanced NSCLC who progress after platinum-doublet chemotherapy (PDC) and immune checkpoint inhibitor therapy, treatment options are limited; DTX is most commonly used in this setting. Preclinical data with CAN, a selective interleukin-1β inhibitor, plus DTX showed greater tumor growth reduction than DTX alone and decreased immunosuppressive cell infiltration in the tumor microenvironment.

Methods

The multicenter phase III CANOPY-2 trial (NCT03626545) evaluated CAN added to DTX in pts with advanced NSCLC. Eligible pts were ≥18 years old, with histologically confirmed stage IIIB-IV (AJCC v8) NSCLC without known EGFR or ALK alterations, who had received 1 prior PDC regimen and 1 prior anti-PD-(L)1 agent, combined or sequentially, for advanced disease. Pts were randomized to subcutaneous CAN 200 mg + intravenous DTX 75 mg/m2 every 3 weeks or placebo (pbo) + DTX. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint.

Results

Overall, 237 pts were randomized: 120 CAN + DTX, 117 pbo + DTX (3 pts did not receive pbo + DTX and were not included in safety analysis). As of Jan 8, 2021, median follow-up was 13.8 months (mo). Patient characteristics were well balanced between treatment arms. The primary endpoint of OS was not met (median 10.5 vs 11.3 mo for CAN vs pbo, respectively; HR 1.06; 95% CI, 0.76-1.48). Median PFS was 4.17 vs 4.21 mo for CAN vs pbo (HR 1.12; 95% CI, 0.85-1.50). Grade ≥3 adverse events (AEs) occurred in 70.0% of pts with CAN vs 69.3% with pbo, including infections in 21.7% vs 17.6% (6.7% vs 1.8% were fatal), neutropenia in 35.0% vs 38.6%, and thrombocytopenia in 3.3% vs 2.7% of pts, respectively. Study drug discontinuation due to AEs was reported in 23.3% vs 28.9% of pts receiving CAN vs pbo, respectively; on-treatment death in 35.8% vs 31.6% of pts.

Conclusions

Addition of CAN to DTX in the 2/3L setting did not improve OS or PFS in pts with advanced NSCLC. Safety profiles were comparable between the 2 arms, but a numerically higher incidence of infections (including fatal infections) occurred with CAN. Biomarker analysis is ongoing.

Clinical trial identification

NCT03626545.

Editorial acknowledgement

Medical editorial assistance was provided by Ana Costa, PhD of Chameleon Communications, London, UK, which was funded by Novartis, East Hanover, NJ, USA.

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

L. Paz-Ares: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Member of the Board of Directors: Altum Sequencing; Financial Interests, Institutional, Other, Coordinating PI: Alkermes; Financial Interests, Institutional, Other, Coordinating PI: Amgen; Financial Interests, Institutional, Other, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Other, Coordinating PI: BMS; Financial Interests, Institutional, Other, Coordinating PI: Daiichi Sankyo; Financial Interests, Institutional, Other, Coordinating PI: IO Biotech; Financial Interests, Institutional, Other, Coordinating PI: Janssen-Cilag International NV; Financial Interests, Institutional, Other, Coordinating PI: Lilly; Financial Interests, Institutional, Other, Coordinating PI: Merck Sharp & Dohme Corp.; Financial Interests, Institutional, Other, Coordinating PI: Novartis; Financial Interests, Institutional, Other, Coordinating PI: Pfizer; Financial Interests, Institutional, Other, Coordinating PI: PharmaMar; Financial Interests, Institutional, Other, Coordinating PI: Roche; Financial Interests, Institutional, Other, Coordinating PI: Sanofi; Financial Interests, Institutional, Other, Coordinating PI: Takeda; Financial Interests, Institutional, Other, Coordinating PI: Tesaro. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Guardant Health Inc.; Financial Interests, Personal, Advisory Board: Illumina; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Thermo Fischer; Non-Financial Interests, Institutional, Other, Local PI: AbbVie; Non-Financial Interests, Institutional, Other, Local PI: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Other, Coordinating PI: Chugai; Non-Financial Interests, Institutional, Other, Local PI: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Local PI: Eli Lilly; Financial Interests, Personal and Institutional, Other, Coordinating PI: Novartis; Financial Interests, Personal and Institutional, Other, Coordinating PI: Pfizer; Non-Financial Interests, Institutional, Research Grant: Preferred Network. W.D.T. Lim: Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Writing Engagements: Roche; Financial Interests, Institutional, Other, Trial Chair: Bristol Myers Squibb; Financial Interests, Institutional, Other, Grant funding for investigator-sponsored study: Bristol Myers Squibb; Financial Interests, Institutional, Other, Steering Committee Member: Novartis. B. Halmos: Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: Elevation; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Personal, Other, Consulting: Merck; Financial Interests, Personal, Other, Consulting: BMS; Financial Interests, Personal, Other, Consulting: Novartis; Financial Interests, Personal, Other, Consulting: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Other, Consulting: TPT; Financial Interests, Personal, Other, Consulting: Apollomics; Financial Interests, Personal, Other, Consulting: Pfizer; Financial Interests, Personal, Other, Consulting: Genentech; Financial Interests, Personal, Other, Consulting: Mirati. B.C. Cho: Financial Interests, Institutional, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal and Institutional, Research Grant: Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Non-Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. C. Zhou: Financial Interests, Personal, Invited Speaker: Lily China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone, Luye Pharma, Top-Alliance Biosciences Inc., Amoy Diagnostics; Financial Interests, Personal, Advisory Role: Innovent Biologics, Hengrui, Qilu, Top-Alliance Biosciences Inc. I. Demedts: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Takeda. A. Atmaca: Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board: Novartis. S. Baka: Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: BMS; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: Lilly. B.P. Mookerjee: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. S. Portella: Financial Interests, Personal, Full or part-time Employment: Novartis. Z. Zhu: Financial Interests, Personal, Full or part-time Employment: Novartis. B. Dharan: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Roche, Samsung Bioepis; Financial Interests, Personal, Other, Consultancy: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Roche, Samsung Bioepis. All other authors have declared no conflicts of interest.

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Mini Oral session

Discussion LBA50, LBA51 & 1194MO

Speakers
  • David R. Gandara (Sacramento, CA, United States of America)
Lecture Time
18:15 - 18:30
Session Name
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 19.09.2021
Time
17:30 - 18:30