Table 4.
Selected therapies under investigation for treatment of locally advanced cervical cancer.
| Therapy | Mechanism of action | Cervical cancer-related health authority designations/decisions | Pivotal trial name/IDs | Study design | Patient population | Treatment arms | Primary endpoint(s) | Primary endpoint completion date | Available pivotal trial efficacy data |
|---|---|---|---|---|---|---|---|---|---|
| Z-100 | Immunomodulator (bacterial extract) | None | Z100–01 NCT02247232 |
Phase III, double-blind randomized | Adults with SCC cervical cancer, FIGO 2008 stage IIIB, not previously treated | Experimental arm:* Z-100 + radiotherapy Control arm: Placebo + radiotherapy |
OS | Expected October 2021 Enrollment completed July 2018 |
None |
| Durvalumab | Anti-PD-L1 antibody | None | CALLA NCT03830866 |
Phase III, double-blind, randomized 1:1 | Adults with SCC, AC, or ASC cervical cancer, FIGO 2009 Stage IB2-IIB node positive or IIIA-IVA any node status, not previously treated | Experimental arm: Durvalumab 1500 mg IV Q4W for 24 cycles + CRT (EBRT + cisplatin 40 mg/m2 IV or carboplatin AUC2 IV, followed by image-guided brachytherapy) once weekly for 5 weeks Control arm: Placebo Q4W for 24 cycles + CRT once weekly for 5 weeks |
PFS by investigator assessment per RECIST v1.1 | Expected October 2022 Enrollment completed January 2021 |
Primary endpoint not met [62] |
| Pembrolizumab | Anti-PD-1 antibody | None | KEYNOTE-A18/ENGOT-cx11/GOG-3047 NCT04221945 |
Phase III, double-blind, randomized 1:1 | Patients with high-risk SCC, AC, or ASC cervical cancer, FIGO 2014 stage IB2-IIB node positive or stage III-IVA any node status, not previously treated | Experimental arm: 5 cycles of pembro 200 mg Q3W + CRT (EBRT + cisplatin 40 mg/m2 IV QW, followed by brachytherapy), followed by 15 cycles of pembro 400 mg Q6W Control arm: Placebo + CRT, followed by placebo Q6W |
PFS by investigator assessment per RECIST v1.1 OS |
Expected February 2024 | None |
Dosing information was not available on the respective clinicaltrials.gov information webpage.
Trial design and anticipated primary endpoint completion dates were obtained from the respective clinicaltrials.gov webpages. Therapies are listed in order of primary endpoint completion date.
AC, adenocarcinoma; ASC, adenosquamous carcinoma; AUC, area under the curve; CRT, chemoradiotherapy; EBRT, external beam radiotherapy; FIGO, International Federation of Gynecology and Obstetrics; IV, intravenous; OS, overall survival; PD-1, programmed cell death-1; PD-L1, programmed cell death ligand-1; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; SCC, squamous cell carcinoma.