Table 2.
Published data on immune checkpoint drug monotherapy for recurrent/metastatic cervical cancer.
| Ref. | Trial | Phase | N | Histology | Patient population | Treatment regimens | Primary endpoint |
|---|---|---|---|---|---|---|---|
| (33) | KEYNOTE-158 NCT02628067 (Multi-location) |
II | 98 | SCC = 93.9% AC = 5.1% ASC = 1.0% |
Advanced CC; progression during or intolerance to ≥1 lines of standard therapy | Pembrolizumab 200 mg IV q3w for up to 2 years | ORR, 12.2% (PD-L1+, 14.6%; PD-L1-, 0%) |
| (39) | KGOG1041 (Korean) |
Retrospective | 117 | SCC = 75.2% AC = 16.2% ASC = 3.4% NEC = 3.4% GCC = 0.9% BSCC = 0.9% |
CC; tumor progression during or after the use of ≥1 lines of chemotherapy | Pembrolizumab 200 mg IV q3w until disease progression, unacceptable toxicity, or patient withdrawal occurred | ORR, 9.4% (ECOG ≤1, 18.9%); Safety: AEs, 55 (47.0%) pts; AEs ≥ grade 3, 8 (6.8%) pts; suspicious treatment-related deaths, 2 of 8 |
| (40) | EMPOWER- Cervical 1/GOG-3016/ENGOT-cx9 NCT03257267 (Multi-location) |
III | Cemiplimab = 304; Chemotherapy = 304 | SCC = 77.8% AC/ASC = 22.2% |
R/M CC; disease progression after first- line platinum-containing chemotherapy |
Cemiplimab 350 mg IV q3w until PD, unacceptable toxicity, or until 96 weeks; The investigator’s choice of single-agent chemotherapy. |
Median OS, 12.0 months vs. 8.5 months; |
| (41) |
NCT03104699 (Multi-location) |
II | 161 | SCC = 62.7% AC = 32.3% ASC = 4.3% Other = 0.6% |
R/M CC; disease progression after first- line platinum-based treatment regimen |
Balstilimab 3mg/kg IV q2w for up to 24 months | ORR, 15% (PD-L1+, 20%; PD-L1-, 7.9%; SCC, 17.6%; AC, 12.5%) |
| (34) | CheckMate 358 NCT02488759 (Multi-location) |
I/II | 19 | SCC = 100% | R/M CC; SCC; HPV+ | Nivolumab 240 mg IV q2w for up to 2 years | ORR, 26.3% |
| (35) | Tamura et al., 2019 (Japan) |
II | 20 | SCC = 70% AC = 25% ASC = 5% |
Advanced or recurrent CC; ≥1 lines previous chemotherapy regimen |
Nivolumab 240 mg IV q2w until CR or PD, unacceptable toxicity, investigator decision, or withdrawal of consent | ORR, 25% (PD-L1+, 33%; PD-L1-, 0%) |
| (32) | NRG-GY002 NCT02257528 (Multi-location) |
II | 25 | SCC = 60.0% AC = 24.0% ASC = 16.0% |
Persistent R/M CC; ≥1 lines prior systemic chemotherapeutic regimen | Nivolumab 3mg/kg IV q2w for a maximum of 46 doses until PD or adverse effects prohibit therapy. | ORR, 4% |
| (42) | Lheureux et al., 2018 (U.S. and Canada) |
I/II | 42 | SCC = 69% AC = 31% |
R/M CC | The run-in cohort (phase 1): Ipilimumab, 3mg/kg IV q3w for 4 cycles; The second cohort (phase 2): Ipilimumab, 10mg/kg IV q3w for 4 cycles followed by 10mg/kg IV q12w for 4 additional cycles as maintenance therapy for pts with radiologic response or stabilization |
ORR, 2.4%; Safety: AEs ≥ Grade 3, 12 pts |
| (43, 44) |
NCT03676959 (China) |
I | Dose-escalation phase = 12 Dose-expansion phase = 92 |
SCC = 95.7% AC = 2.1% ASC = 1.1% Other = 1.1% |
R/M CC; previously failed or intolerant to the first-line platinum-based regimen | Socazolimab 5mg/kg IV q2w until PD | ORR, 15.4% (PD-L1+, 16.7%; PD-L1-, 17.9%); Safety: MTD was not determined at the highest dose (15 mg/kg); No treatment-related deaths |
| (45) | AK104-201 Wu et al., 2022 (China) |
II | 111 | SCC = 92.8% | R/M CC; progressed on or after two or fewer previous doublet chemotherapy with or without bevacizumab | Cadonilimab 6 mg/kg IV q2w | ORR, 33.0% (PD-L1+, 43.8%) |
| (46, 47) |
NCT03427411 (U.S.) |
II | 59 | CC = 55.9% | Locally advanced or metastatic HPV associated malignancies including: Non-Neuroendocrine CCs |
Bintrafusp alfa 1200mg IV q2w until PD, unacceptable toxicity, or study withdrawal | ORR, 30.5% |
| (38) |
NCT05171790 (China) |
Ib | 53 | SCC = 83% AC = 17% |
R/M CC | QL1706 5.0 mg/kg IV q3w for up to 24 months | ORR, 28% |
R/M, recurrent or metastatic; CC, cervical cancer; SCC, squamous cell carcinoma; AC, adenocarcinoma; ASC, adenosquamous carcinoma; NEC, neuroendocrine cell carcinoma; GCC, Glassy cell carcinoma; BSCC, basaloid squamous cell carcinoma; ECOG, Eastern Cooperative Oncology Group performance status; HPV, human papillomavirus; IV, intravenous; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; CR, complete response; PD, progressive disease; AEs, adverse events; pts, patients; MTD, maximum tolerated dose; CPS, combined positive score; q2w/q3w/q12w, once every two/three/twelve weeks.