Table 5.
Ongoing phase 3 trials of pembrolizumab in patients with breast and gynecologic cancers
| Indication | Trial name | Trial setting | Treatments | Total N (estimated) | Primary endpoints | Key secondary endpoints |
|---|---|---|---|---|---|---|
| TNBC | KEYNOTE-242/S1418/BR006 [116] | Early-stage with residual invasive cancer or positive lymph nodes after neoadjuvant chemotherapy | Pembrolizumab (adjuvant) vs observation | 1155 |
Invasive disease-free survival Severity of fatigue Physical function |
OS Distant recurrence-free survival Safety |
| HR+/HER2− breast cancer | KEYNOTE-756a [117, 118] | High-risk, early-stage | Pembrolizumab + chemotherapy (neoadjuvant) followed by pembrolizumab + endocrine therapy (adjuvant) vs placebo + chemotherapy (neoadjuvant) followed by placebo + endocrine therapy (adjuvant) | 1240 |
pCR (ypT0/Tis ypN0) EFS |
OS pCR (other definitions) EFS and OS in PD-L1 CPS ≥ 1 Safety HRQoL |
| HR+/HER2− breast cancer | KEYNOTE-B49 [120, 121] | Late-stage (locally recurrent inoperable or metastatic), PD-L1 CPS ≥ 1 | Pembrolizumab + chemotherapy vs placebo + chemotherapy after progression on prior endocrine therapy | 800 |
PFS (BICR) in PD-L1 CPS ≥ 10 and ≥ 1 OS in PD-L1 CPS ≥ 10 and ≥ 1 |
PFS (investigator), ORR (BICR), DCR (BICR), and DOR (BICR) in PD-L1 CPS ≥ 10 and ≥ 1 Safety HRQoL |
| Endometrial cancer | KEYNOTE-B21/ENGOT-en11/GOG-3053b [122] | Newly diagnosed, high-risk (stage 1/II nonendometrioid, stage III/IVA, p53 abnormality) | Pembrolizumab + chemotherapy ± radiotherapy (adjuvant) vs placebo + chemotherapy ± radiotherapy (adjuvant) following surgery with curative intent with no postoperative evidence of disease | 990 |
DFS (investigator) OS |
DFS (BICR) DFS (investigator) and OS by biomarker status (PD-L1 and TMB) Safety HRQoL |
| Endometrial cancer | KEYNOTE-C93/GOG-3064/ENGOT-en15 [124] | Previously untreated, dMMR, advanced (stage III–IV) or recurrent | Pembrolizumab vs chemotherapy | 350 |
PFS (BICR) OS |
ORR, DCR, and DOR (all BICR) PFS (investigator) PFS after subsequent-line treatment (investigator) Safety HRQoL |
| Ovarian cancer | KEYLYNK-001/ENGOT-ov43/GOG-3036 [127] | Advanced (stage III–IV), BRCA1/2-nonmutated | Pembrolizumab + chemotherapy followed by pembrolizumab + olaparib vs pembrolizumab + chemotherapy followed by pembrolizumab + placebo vs placebo + chemotherapy followed by placebo | 1367 |
PFS (investigator) OS |
PFS (BICR) PFS after subsequent-line treatment (investigator) Safety HRQoL |
| Ovarian cancer | KEYNOTE-B96/ENGOT-ov65 [128] | Platinum-resistant | Pembrolizumab + paclitaxel (± bevacizumab) vs placebo + paclitaxel (± bevacizumab) | 616 | PFS (investigator) in PD-L1 CPS ≥ 1 and all patients |
OS in PD-L1 CPS ≥ 1 and all patients PFS (BICR) in PD-L1 CPS ≥ 1 and all patients Safety HRQoL |
| Ovarian cancer | ARTISTRY-7 [129] | Platinum-resistant | Pembrolizumab + nemvaleukin alfa vs chemotherapy (PLD, paclitaxel, topotecan, or gemcitabine) | 376 | PFS (investigator) |
ORR (investigator) OS DCR, DOR, and TTR (all investigator) Safety |
BICR blinded independent central review, CPS combined positive score, CR complete response, DCR disease control rate, DFS disease-free survival, ENGOT European Network of Gynaecological Oncological Trial groups, dMMR mismatch repair deficient, DOR duration of response, EFS event-free survival, GOG GOG Foundation, Inc., HER human epidermal growth factor receptor 2, HR hormone receptor, HRQoL health-related quality of life, ORR objective response rate, OS overall survival, pCR pathologic complete response, PD-L1 programmed cell death ligand 1, PFS progression-free survival, PLD pegylated liposomal doxorubicin, pMMR mismatch repair proficient, TMB tumor mutational burden, TNBC triple-negative breast cancer, TTR time to response
aPositive results from the first interim analysis demonstrating a significant improvement in pCR were reported at the European Society for Medical Oncology (ESMO) Congress in 2023 [119]. A full description of the trial results is expected in future publications
bResults from an interim analysis were recently published [123]. The study did not meet its primary endpoint in all-comers; however, prespecified subgroup analysis based on the study's stratification factors suggested clinically relevant improvement for patients with dMMR tumors