655O - Phase Ib study of cofetuzumab pelidotin, an anti-PTK7 antibody-drug conjugate, in patients with PTK7-expressing recurrent non-small cell lung cancer (rNSCLC)

Background

Cofetuzumab pelidotin (Cofe-P), a protein tyrosine kinase 7 (PTK7)–targeting antibody-drug conjugate, was tolerable and had preliminary antitumor activity in patients (pts) with advanced solid tumors (Phase 1; NCT02222922). Results are presented from an ongoing Phase 1b, open-label, single-arm, multicenter study (NCT04189614) of Cofe-P in pts with PTK7-expressing rNSCLC.

Methods

Eligible pts were ≥18 yrs with PTK7-expressing (central immunohistochemistry [IHC]) rNSCLC and prior platinum doublet and immune checkpoint inhibitor (tumors w/o actionable genetic alterations [AGA−]) or platinum doublet and targeted agent(s) (AGA+ tumors). Pts received 2.8 mg/kg Cofe-P IV Q3W until PD/unacceptable toxicity.

Results

As of August 9, 2022, 56 pts received Cofe-P (median age, 64 years; male, 63%; Asian, 50%, White, 46%); 27 pts (48%) were nonsquamous (NSQ) EGFR WT, 13 (23%) were NSQ EGFR mutant, and 16 (29%) were squamous (SQ). PTK7 IHC enrollment cutoff was refined during study; 42 pts (75%) had PTK7 expression above final ≥90%/≥2+ cutoff; of these, 21 (50%) were NSQ EGFR WT. Enrollment of SQ and NSQ EGFR mutant pts was halted to prioritize NSQ EGFR WT accrual due to response rates in each subgroup. Efficacy results are shown in the table. TEAEs were reported in all pts, most common (≥30%): alopecia (52%), neutropenia (45%), headache (36%), pruritis (36%), and decreased appetite (30%). Grade ≥3 TEAEs were reported in 68% of pts, most common (≥5%): neutropenia (39%), leukopenia (9%), pneumonia (7%), anemia (5%), fatigue (5%). Peripheral neuropathy was reported in 18% of pts; 2% had Grade 3. No deaths related to Cofe-P were reported. PK was similar to previous phase 1 study with Cofe-P conjugate elimination half-life ∼3 days. Table: 655O

^aResponse-evaluable pts (N=20) (≥1 postbaseline measurement). CI, confidence intervals; CBR, clinical benefit rate; CR, complete response; EGFR, epidermal growth factor; mDOR, median duration of response; mPFS, median progression free survival; NSQ, nonsquamous; ORR, objective response rate; PR, partial response; PTK7, protein tyrosine kinase 7; pts, patients; SD, stable disease; WT, wild type.

Conclusions

Cofe-P was well-tolerated with encouraging antitumor activity observed in rNSCLC and 30% ORR in the subpopulation with NSQ EGFR WT NSCLC and PTK7 ≥90%/≥2+.

Clinical trial identification

NCT02222922.

Editorial acknowledgement

Medical writing support was provided by Caryne Craige, PhD, of Fishawack Facilitate Ltd., and funded by AbbVie.

Legal entity responsible for the study

AbbVie.

Funding

AbbVie and Pfizer provided financial support for the Ph 1b study and an AbbVie/Pfizer Joint Steering Committee oversaw design and conduct of Ph 1b study. AbbVie provided support for analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.

Disclosure

B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc.; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., Bridgebio therapeutics, KANAPH Therapeutic Inc., Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Founder: DAAN Biotherapeutics. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, Seagen, VBL Therapeutics, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, Black Diamond, BeiGene, BerGenBio, BioAtla, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Jounce Therapeutics, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Rain Therapeutics, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Sanofi, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics. J. Bar: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Bayer, BMS, Causalis, Eisai, MSD, Novartis, Roche, Takeda; Financial Interests, Institutional, Research Funding: ImmuneAI, OncoHost, MSD, AstraZeneca. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi sankyo, Lilly, Boehringer Ingelheim, Amgen, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Lilly, Daiichi sankyo, AbbVie, Taiho, MSD, Takeda, Amgen, Boehringer Ingelheim, Chugai; Financial Interests, Personal, Steering Committee Member: AstraZeneca. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost; Financial Interests, Personal, Stocks/Shares: Nixio; Financial Interests, Institutional, Research Grant: BMS. M.T. Moskovitz: Financial Interests, Institutional, Research Funding: AstraZeneca; Non-Financial Interests, Institutional, Other, Honorarium: BMS, MSD, Roche, AstraZeneca, Merck, AbbVie, Takeda, Novartis, Amgen; Financial Interests, Personal, Other, Consulting Fees: MSD, Takeda, Bayer, Amgen. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck, Pfizer, Lilly, BMS/Ono, Takeda, Janssen, IMBdx; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck, Lilly, Amgen; Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Lunit. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Institutional, Local PI, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer BeiGene BioInvent International AB, BMS, Boehringer, Boheringer, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith: Multiple. M.J. De Miguel Luken: Financial Interests, Institutional, Invited Speaker: Janssen, MSD; Non-Financial Interests, Principal Investigator: Janssen, MSD, Roche, PharmaMar, Replimune, Novartis, AbbVie, Achilles, Amunix, Arcus, Furmo, BioNTech, Catalym, Dizal, Genentech, Loxo, Numab, Seagen. Y. Okuma: Financial Interests, Personal, Invited Speaker: AstraZeneca, K. K., Nippon Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Eli Lilly K. K., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc.; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Local PI: AbbVie, G.K., Chugai Co., Ltd.; Financial Interests, Personal, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: MSD. P.J. Ansell, C. Biesdorf de Almeida, R. Saab, K. Freise, D. Ramies, E. Jeng: Financial Interests, Personal, Full or part-time Employment: AbbVie; Financial Interests, Personal, Stocks/Shares: AbbVie. D.R. Camidge: Financial Interests, Institutional, Principal Investigator: AbbVie, AstraZeneca, Blueprint, Dizal, Inhibrx, Karyopharm, Nuvalent, Pfizer, Phosplatin, Psioxus, Rain, Roche/Genentech, Seattle Genetics, Takeda, Turning Point, Verastem; Financial Interests, Personal, Advisory Board: AbbVie, Anheart, Appolomics, AstraZeneca/ Daiichi Sankyo, BeiGene, EMD Serono, Elevation, Hummingbird, Janssen, Medtronic, Mersana, Mirati, Nalo Therapeutics, Onkure, Regeneron, Roche/Genentech, Sanofi, Takeda, Theseus, Xcovery, Amgen, AstraZeneca, Bio-Thera, Blueprint, Daiichi Sankyo, Hengrui, Eli Lilly, Dizal, Helsinn, Kestrel, Nuvalent, Puma, Ribon, Seattle Genetics, Turning Point. All other authors have declared no conflicts of interest.