Abstract CT256: Results from KEYNOTE-B98: A phase 1b/2 study of pembrolizumab plus investigational agents in patients with anti-PD-(L)1-refractory extensive-stage small-cell lung cancer (ES-SCLC)
Bibliographic record
Abstract
Abstract Background: Anti-PD-L1 plus chemotherapy is a recommended first-line (1L) treatment option for ES-SCLC. However, most patients (pts) relapse and effective second-line (2L) treatment options are limited. Pembrolizumab (pembro) has demonstrated antitumor activity in previously treated ES-SCLC. The KEYNOTE-B98 study (NCT04938817) evaluated pembro in combination with investigational agents as 2L therapy for anti-PD-(L)1-refractory ES-SCLC. We present initial results from this study. Methods: This randomized, phase 1b/2, multicenter, open-label, platform study enrolled adult pts with confirmed ES-SCLC (stage IV per AJCC v8.0) that progressed ≤12 wk of last anti-PD-(L)1 dose given as part of 1L platinum-based therapy, measurable disease per RECIST v1.1, and ECOG PS of 0-1. Pts were randomized 1:1:1:1 to: (A) MK-1308A (coformulation of quavonlimab [anti-CTLA4] 25 mg + pembro 400 mg) Q6W, (B) MK-1308A Q6W + lenvatinib 20 mg QD, (C) MK-1308A Q6W + MK-4830 (anti-ILT4) 800 mg Q3W, and (D) MK-4280A (coformulation of favezelimab [anti-LAG3] 800 mg + pembro 200 mg) Q3W. A safety lead-in was performed for the first 21 days of treatment in cohort C in ≤10 pts evaluable for dose-limiting toxicities (DLTs), followed by efficacy evaluation. Pts in safety lead-in were not randomized. Primary endpoints were safety (DLTs in safety lead-in phase, AEs, and discontinuations due to AEs) and ORR per RECIST v1.1 by BICR. Secondary endpoints were PFS and DOR per RECIST v1.1 by BICR. Results: 76 pts received ≥1 dose of study treatment: cohort A, n = 19; B, n = 20; C, n = 17; D, n = 20. Median follow-up at data cutoff (Jul 3, 2023) was 12.9 (range, 5.9-21.8) mo. During safety lead-in, 1 pt had a DLT of grade 3 arthralgia. Treatment-related AEs (TRAEs) occurred in 12 pts (63%; grade 3/4, n = 2, 11%) in cohort A, 17 (85%; grade 3/4, n = 6, 30%) in cohort B, 12 (71%; grade 3/4, n = 1, 6%) in cohort C, and 15 (75%; grade 3/4, n = 4, 20%) in cohort D; none were grade 5. 1 pt (5%) in cohort A, 3 (15%) in cohort B, 0 in cohort C, and 2 (10%) in cohort D had TRAEs that led to treatment discontinuation. Confirmed ORR (95% CI) was 5% (0%-26%; 1 PR) in cohort A, 25% (9%-49%; 5 PR) in cohort B, 0% (0%-20%) in cohort C, and 0% (0%-17%) in cohort D. Median (range) DOR was not reached (9.4+ to 9.4+ mo) in group A and 3.9 (2.0-3.9) mo in group B. Median (95% CI) PFS was 1.4 (1.2-2.6) mo, 3.9 (1.7-5.3) mo, 1.2 (0.8-1.4) mo, and 2.6 (1.4-4.0) mo in cohorts A-D, respectively. Conclusions: In the KEYNOTE-B98 study of anti-PD-(L)1-refractory ES-SCLC, no new safety signals were identified for the pembro-based combinations investigated. Modest antitumor activity was observed with MK-1308A ± lenvatinib, but no activity for MK-1308A + MK-4830 or for MK-4280A. This study provided proof-of-concept for the feasibility of platform trials in 2L ES-SCLC. Further investigation of new compounds and combinations is needed in this population. Citation Format: Alejandro Navarro, Myung-Ju Ahn, James Stevenson, Nir Peled, Talia Shentzer Kutiel, Florian Huemer, Dong-Wan Kim, Maria Jove Casulleras, Adnan Khattak, Dariusz Kowalski, Natasha B. Leighl, Filippo de Marinis, Carolin Lips, Jiaxin Niu, Mo Huang, Bin Zhao, Hazem El-Osta, Taofeek Owonikoko. Results from KEYNOTE-B98: A phase 1b/2 study of pembrolizumab plus investigational agents in patients with anti-PD-(L)1-refractory extensive-stage small-cell lung cancer (ES-SCLC) [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 CT256.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".