Abstract CT249: Results from KEYMAKER-U01 substudy 3: a phase 2 umbrella study of pembrolizumab plus investigational agents in patients with non-small-cell lung cancer (NSCLC) previously treated with anti-PD-(L)1 therapy
Authors: Aggarwal Charu , Stevenson James , Kowalski Dariusz M. , Csőszi Tibor , Peled Nir , Cho Byoung Chul , Rubio-Viqueira Belén , Niu Jiaxin , Carbone David P. , Arnold Susanne M. , Awad Mark M. , Gainor Justin F. , Rao Suman , Tsao Anne S. , Zhou Heng , Akala Omobolaji O. , Chartash Elliot , Nadal Ernest 
Published: April 2024

Abstract
Background: The anti-PD-1 monoclonal antibody (mAB) pembrolizumab with or without chemotherapy is a standard of care for first-line advanced or metastatic NSCLC and as monotherapy for NSCLC with PD-L1 TPS ≥1% previously treated with chemotherapy. However, there are limited treatment options for patients whose disease progresses after anti-PD-(L)1 therapy. We present results from the KEYMAKER-U01 study (NCT04165798) substudy 3, which evaluated pembrolizumab in combination with investigational mAbs for patients with NSCLC previously treated with anti-PD-(L)1 therapy.
Methods: This randomized, phase 2, rolling-arm, multicenter, open-label, adaptive-design study enrolled patients aged ≥18 y with ECOG PS of 0 or 1 and confirmed stage IV squamous or nonsquamous NSCLC (per current AJCC) who progressed on or after prior anti-PD-(L)1 therapy and platinum-based chemotherapy given sequentially or concomitantly. Patients were randomized to receive up to 35 cycles (~2 y) of pembrolizumab 200 mg Q3W plus either the anti-CD27 mAb boserolimab 30 mg Q3W (arm A), the anti-ILT4 mAb MK-4830 800 mg Q3W (arm B), or the anti-ILT3 mAb MK-0482 750 mg Q3W (arm C). The primary endpoint was ORR per RECIST version 1.1 by investigator review. Secondary endpoints were PFS per RECIST version 1.1 by investigator review and safety (AEs and treatment discontinuation due to AEs).
Results: Overall, 127 patients received ≥1 dose of study treatment in arms A (n = 37), B (n = 45), and C (n = 45). At data cutoff (Nov 10, 2023), median study follow-up was 35 (range, 31-45) mo, 33 (range, 30-36) mo, and 23 (range, 18-25) mo, respectively. ORR (95% CI) was 8% (2%-22%; 1 CR, 2 PR) in arm A, 11% (4%-24%; 1 CR, 4 PR) in arm B, and 4% (1%-15%; 0 CR, 2 PR) in arm C. Median (95% CI) PFS was 2.4 (1.4-2.8) mo, 2.4 (1.5-2.7) mo, and 2.6 (1.4-4.7) mo, respectively. AEs of any cause occurred in 37 patients (100%) in arm A, 42 (93%) in arm B, and 41 (91%) in arm C. These were grade 3-5 in 21 (57%), 20 (44%), and 17 patients (38%), respectively. Treatment-related AEs occurred in 27 patients (73%; grade 3/4, 16%) in arm A, 25 patients (56%; grade 3/4, 9%) in arm B, and 23 patients (51%; grade 3/4, 11%) in arm C. Six (16%), 8 (18%), and 3 patients (7%) discontinued treatment due to any AE. Grade 5 AEs occurred in 2 (5%), 4 (9%), and 2 patients (4%), respectively; none were deemed to be treatment related.
Conclusions: In the KEYMAKER-U01 substudy 3 evaluating novel treatment combinations of pembrolizumab plus boserolimab, MK-4830, or MK-0482 in patients with NSCLC that progressed on/after platinum-based chemotherapy and anti-PD-(L)1 therapy, modest antitumor activity was observed with all 3 treatment combinations. No new safety signals were observed for the treatment combinations investigated.
Citation Format: Charu Aggarwal, James Stevenson, Dariusz M. Kowalski, Tibor Csőszi, Nir Peled, Byoung Chul Cho, Belén Rubio-Viqueira, Jiaxin Niu, David P. Carbone, Susanne M. Arnold, Mark M. Awad, Justin F. Gainor, Suman Rao, Anne S. Tsao, Heng Zhou, Omobolaji O. Akala, Elliot Chartash, Ernest Nadal. Results from KEYMAKER-U01 substudy 3: a phase 2 umbrella study of pembrolizumab plus investigational agents in patients with non-small-cell lung cancer (NSCLC) previously treated with anti-PD-(L)1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT249.