Nivolumab plus rucaparib for metastatic castration-resistant prostate cancer: results from the phase 2 CheckMate 9KD trial
Bibliographic record
Abstract
Background CheckMate 9KD ( NCT03338790 ) is a non-randomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib. Methods CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0–1. Cohort A1 included patients with postchemotherapy mCRPC (1–2 prior taxane-based regimens) and ≤2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naïve mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 mg every 4 weeks plus rucaparib 600 mg two times per day (nivolumab dosing ≤2 years). Coprimary endpoints were objective response rate (ORR) per Prostate Cancer Clinical Trials Working Group 3 and prostate-specific antigen response rate (PSA 50 -RR; ≥50% PSA reduction) in all-treated patients and patients with homologous recombination deficiency (HRD)-positive tumors, determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. Results Outcomes (95% CI) among all-treated, HRD-positive, and BRCA1/2 -positive populations for cohort A1 were confirmed ORR: 10.3% (3.9–21.2) (n=58), 17.2% (5.8–35.8) (n=29), and 33.3% (7.5–70.1) (n=9); confirmed PSA 50 -RR: 11.9% (5.9–20.8) (n=84), 18.2% (8.2–32.7) (n=44), and 41.7% (15.2–72.3) (n=12); median rPFS: 4.9 (3.7–5.7) (n=88), 5.8 (3.7–8.4) (n=45), and 5.6 (2.8–15.7) (n=12) months; and median OS: 13.9 (10.4–15.8) (n=88), 15.4 (11.4–18.2) (n=45), and 15.2 (3.0–not estimable) (n=12) months. For cohort A2 they were confirmed ORR: 15.4% (5.9–30.5) (n=39), 25.0% (8.7–49.1) (n=20), and 33.3% (7.5–70.1) (n=9); confirmed PSA 50 -RR: 27.3% (17.0–39.6) (n=66), 41.9 (24.5–60.9) (n=31), and 84.6% (54.6–98.1) (n=13); median rPFS: 8.1 (5.6–10.9) (n=71), 10.9 (6.7–12.0) (n=34), and 10.9 (5.6–12.0) (n=15) months; and median OS: 20.2 (14.1–22.8) (n=71), 22.7 (14.1–not estimable) (n=34), and 20.2 (11.1–not estimable) (n=15) months. In cohorts A1 and A2, respectively, the most common any-grade and grade 3–4 treatment-related adverse events (TRAEs) were nausea (40.9% and 40.8%) and anemia (20.5% and 14.1%). Discontinuation rates due to TRAEs were 27.3% and 23.9%, respectively. Conclusions Nivolumab plus rucaparib is active in patients with HRD-positive postchemotherapy or chemotherapy-naïve mCRPC, particularly those harboring BRCA1/2 mutations. Safety was as expected, with no new signals identified. Whether the addition of nivolumab incrementally improves outcomes versus rucaparib alone cannot be determined from this trial. Trial registration number NCT03338790 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".