746MO - Randomized phase II trial of durvalumab in combination with olaparib and cediranib (DOC) compared to olaparib and cediranib (OC) or durvalumab and cediranib (DC) or standard of care chemotherapy (SOC) in platinum-resistant ovarian cancer with prior bevacizumab (NRG-GY023)

Background

In platinum-resistant ovarian cancer, non-platinum chemotherapy is the standard of care after progression on combination bevacizumab and chemotherapy. We assessed the activity of DOC, DC or OC compared to SOC in bevacizumab pre-exposed population.

Methods

NRG-GY023 is an open-label, randomized, phase II trial conducted in the United States with a targeted sample size of 164 patients (pts). Eligibility included high-grade serous/endometrioid, or clear cell platinum-resistant ovarian cancer with 2-5 prior systemic therapies. Prior use of bevacizumab is required. Treatments were randomly assigned 1:2:2:2 to SOC (weekly paclitaxel, topotecan or liposomal doxorubicin), DOC, DC or OC. The primary end point was progression-free survival (PFS). Secondary end points included overall survival and overall response rate. Interim futility analysis was planned when 28 PFS events (60% information) were available in any pair of one experimental arm with the SOC; arms with a hazard ratio (HR) estimate (ref: SOC) > 0.87 would be discontinued.

Results

By the data cutoff (10/31/2022), 120 pts were enrolled with a median age 65 yo [IQR: 58-69] and 10% were with germline or somatic BRCA mutation. All received prior bevacizumab in either the upfront or recurrent setting. Other prior therapies included PARP inhibitor (49%) and immunotherapy (11%). 103 pts were treated (15 SOC, 30 DOC, 28 DC, and 30 OC, respectively). At the data cutoff, median follow-up time was 4.3 months (IQR: 2.0-7.9). Median PFS was 4.2 (95% CI, 1.9-5.0), 2.6 (95% CI, 2-4.2), 2.3 (95% CI, 2-4.6), and 2.3 (95% CI, 2.1-3.9) months with SOC, DOC, DC and OC, respectively. The HR estimates (ref: SOC) were 1.01 (95% CI, 0.44-2.31), 1.21 (95% CI, 0.52-2.84), and 1.34 (95%CI, 0.58-3.08) for DOC, DC and OC, respectively. Hematologic adverse events were more common with SOC. Safety signals were consistent with past experience.

Conclusions

None of the experimental arms improved PFS compared with SOC. SOC was active in this heavily pretreated population.

Clinical trial identification

NCT04739800.

Editorial acknowledgement

Legal entity responsible for the study

NRG Oncology.

Funding

United States NCI Cancer Therapy Evaluation Program, NRG Oncology and AstraZeneca.

Disclosure

J. Lee: Financial Interests, Institutional, Research Funding: AstraZeneca, Acrivon Therapeutics; Non-Financial Interests, Personal, Advisory Board: Acrivon Therapeutics; Non-Financial Interests, Personal, Advisory Role: Genentech/Roche. C. Washington: Financial Interests, Institutional, Research Funding: American Cancer Society, Bristol Myers Squibb Foundation; Non-Financial Interests, Personal, Advisory Board: Immunogen. C. Shah, K.N. Moore, J.F. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca. D.S. Miller: Financial Interests, Institutional, Research Funding: AstraZeneca. All other authors have declared no conflicts of interest.