Abstract 1185TiP
Background
The epidermal growth factor receptor (EGFR) is a potent oncogene overexpressed and/or mutated in various solid tumors including non-small cell lung cancer (NSCLC). ABBV-637 is an investigational agent that targets EGFR on tumor cells and delivers a targeted payload that specifically inhibits the pro-survival factor Bcl-xL. This first-in-human trial evaluates the safety and efficacy of ABBV-637 as a monotherapy and in combination with docetaxel (DTX) or osimertinib (Osi) in patients (pts) with advanced or relapsed and refractory (RR) solid tumors.
Trial design
This phase I, open-label trial (NCT04721015) consists of 3 parts (Table). Eligible pts are aged ≥18 years, have measurable disease per RECIST v1.1, and Eastern Cooperative Oncology Group performance status ≤1. Additional criteria for each part are presented in Table. Primary endpoints are: adverse events (including dose-limiting toxicities); recommended phase II dose of ABBV-637 alone; maximum tolerated or administered dose of ABBV-637 plus DTX or Osi; and objective response rate (ORR) of ABBV-637 plus DTX or Osi. Secondary endpoints include: ORR of ABBV-637 alone; duration of response and pharmacokinetics of ABBV-637 alone and combined with DTX or Osi; and progression-free survival and overall survival of ABBV-637 plus DTX or Osi. ABBV-637 is administered intravenously (IV) in 28-day (D) cycles. In Part 2, pts receive an IV infusion of DTX (35 mg/m2 D1, D8, D15) plus IV ABBV-637 (at dose determined in part 2a) in 28-D cycles. In Part 3, pts receive daily oral Osi (80 mg) plus IV ABBV-637 (at dose determined in part 3a). Planned enrollment will be approximately 109 pts (Part 1, n=11; Parts 2 and 3, n=49 each [dose escalation, n=9; expansion, n=9]). Enrollment initiated in March 2021, with Part 1 dose escalation completed. Enrollment for Parts 2/3 combination dose escalation began in January 2022. Table: 1185TiP
| Study part | Treatment | Eligibility |
| Part 1 Dose escalation | ABBV-637 | RR solid tumors Progressed on standard-of-care chemotherapy, radiation, immunotherapy, or targeted therapy |
| Part 2 2a: dose escalation 2b: dose expansion | ABBV-637 + DTX | EGFR*-expressing RR NSCLC Progressed on platinum-based chemotherapy and an immune checkpoint inhibitor or targeted therapy Has not received single-agent chemotherapy |
| Part 3 3a: dose escalation 3b: dose expansion | ABBV-637 + Osi | Mutated EGFR-expressing RR NSCLC Progressed on Osi |
| *Per central laboratory testing by immunohistochemistry. |
Clinical trial identification
NCT04721015.
Editorial acknowledgement
AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Disclosure
J. Rotow: Financial Interests, Institutional, Advisory Role: AstraZeneca, AbbVie, Gritstone, Lilly, Takeda, Sanofi Genzyme; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, Pfizer, Merck, Janssen, Sanofi Genzyme, Jazz Pharmaceuticals, Lilly. K. Yoh: Financial Interests, Institutional, Research Grant: AstraZeneca, Eli Lilly, Pfizer, Daiichi Sankyo, AbbVie, Taiho, Takeda, and MSD; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Janssen, Eli Lilly, Taiho, Novartis, Kyowa Kirin, and Boehringer Ingelheim. T. Shimizu: Financial Interests, Institutional, Research Grant: Novartis, Eli Lilly, Daiichi Sankyo, AbbVie, Bristol Myers Squibb, Eisai, AstraZeneca, Pfizer, Loxo Oncology, Takeda Oncology, Incyte, Chordia Therapeutics, 3D Medicines, SymBio Pharmaceuticals, PharmaMar, Five Prime, Astellas; Speaker’s bureau personal f; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo, AbbVie, Takeda Oncology. R. Perets: Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Institutional, Advisory Role: Karyopharm therapeutics, Simplivia, and Gilboa Therapeutics. L. Paz-Ares: Financial Interests, Institutional, Research Grant: MSD, AstraZeneca, Pfizer, BMS; Financial Interests, Institutional, Advisory Role: Lilly, MSD, Roche, PharmaMar, Merck, AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, bayer, BMS, Mirati, GSK, Janssen, Takeda; Financial Interests, Institutional, Funding: AstraZeneca, Janssen, Merck, Mirati. A. Phillips, A. Souers, P.J. Ansell,J. Jin, M. Badawi, R. Saab, G. Morrison-Thiele, S. Jeffries M.R. Neagu Aristide: Financial Interests, Institutional, Full or part-time Employment: AbbVie. B.A. Carneiro: Financial Interests, Institutional, Research Grant: AbbVie, Bayer, AstraZeneca, MedImmune, Astellas, Actuate Therapeutics, Pfizer, Dragonfly Therapeutics; Financial Interests, Institutional, Advisory Role: Foundation Medicine, Tempus, G1 Therapeutics, Seattle Genetics. K.P. Papadopoulos: Financial Interests, Institutional, Advisory Role: Basilia, Turning Point Therapeutics, Bicycle Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, MedImmune, Daiichi Sankyo, Regeneron, Amgen, Calithera Biosciences, Incyte, Merck, Peloton Therapeutics, ADC Therapeutics, 3D Medicines, EMD Serono, Syros Pharmaceuticals, Mersana, MabSpace Biosciences, Jounce Therapeutics, Bayer, Anheart, F-sta. All other authors have declared no conflicts of interest.