(Gynecologic Cancers) Imfinzi + Lynparza + Cediranib Efficacy?
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On July 25, 2019, Alexandra S. Zimmer published in the Journal for ImmunoTherapy of Cancer the efficacy and safety results of a Phase 1 clinical trial evaluating anti-PD-L1 antibody Imfinzi (durvalumab) + PARP inhibitor Lynparza (olaparib) + VEGFR-1/2/3 inhibitor Cediranib (AZD2171) in recurrent gynecologic cancer patients.
The Phase 1 clinical trial enrolled recurrent gynecologic cancer patients including ovarian cancer, endometrial cancer, and triple-negative breast cancer (N=9) with 4-week cycles: Imfinzi 1500mg + Lynparza 300mg twice daily + Cediranib 15–20mg on days 1–5 weekly. The primary endpoint was objective response rate, along with Phase 2 recommended dose evaluation.
This trial was based on previous data showing that the PARP inhibitor Lynparza combined with VEGFR inhibitor Cediranib had higher anti-tumor efficacy compared to Lynparza alone in treatment-resistant recurrent ovarian cancer patients. Immune checkpoint inhibitors also showed good results across cancer types, but gynecologic cancer outcomes had room for improvement. Based on this rationale, the trial combined anti-PD-L1 antibody + PARP inhibitor + VEGFR-1/2/3 inhibitor.
Patient Characteristics:
- Median age: 59 years (range 44–73)
- BRCA mutation: 1 patient; wild-type: 7 patients; unknown: 1 patient
- ECOG 0: 3 patients; ECOG 1: 6 patients
- Median prior treatment regimens: 2
- Prior PARP inhibitor: 0 patients; prior Avastin: 2 patients
- Cancer types: ovarian cancer 7, endometrial cancer 1, triple-negative breast cancer 1
Results: Grade 3–4 adverse events included hypertension (1 patient), anemia (1 patient), and lymphocyte reduction (3 patients). No patients experienced dose-limiting toxicity. The Phase 2 recommended dose was: Imfinzi 1500mg + Lynparza 300mg twice daily + Cediranib 20mg on days 1–5 weekly in 4-week cycles. The objective response rate was 44%, including 4 partial responses and 3 stable disease, with a clinical benefit rate of 67%.
Based on Phase 1 trial results, Alexandra S. Zimmer concluded that recurrent gynecologic cancer patients treated with Imfinzi + Lynparza + Cediranib showed good anti-tumor efficacy with manageable adverse events, supporting progression to Phase 2 clinical trial for continued efficacy verification.
Source: A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1–3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses (J Immunother Cancer. 2019 Jul 25;7(1):197. doi: 10.1186/s40425-019-0680-3.)
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