Prolgolimab Triplet Shows Encouraging Efficacy/Safety in Advanced Cervical Cancer

Treatment with prolgolimab (BCD-100) in combination with chemotherapy and bevacizumab (Avastin) showed auspicious efficacy and an adequate safety profile in patients with recurrent or metastatic cervical cancer, according to findings from the phase 2 CAESURA clinical trial (NCT03912402).¹

As a fully human monoclonal igG1 antibody, prolgolimab interferes with the communication between PD-1 and its ligands PD-L1 and PD-L2, which leads to reduction in tumor size. In a prior phase 1 study (NCT03050047) of prolgolimab monotherapy in an advanced solid tumor population, the efficacy, safety, and pharmacokinetics of prolgolimab were illustrated, particularly in patients with advanced melanoma.² According to phase 2 CAESURA study investigators led by Lyudmila Zhukova, MD, PhD of Moscow Clinical Scientific Center, other potential indications for prolgolimab include non–small cell lung cancer and cervical cancer.¹

In the multicenter, open-label, single-arm, phase 2 CAESURA study, 58 patients with recurrent or metastatic cervical cancer who were 18 years of age or older were enrolled. Patients received up to 6 cycles of treatment with the combination. Prolgolimab was administered at 3 mg/kg along with bevacizumab 15 mg/kg and platinum-based chemotherapy consisting of paclitaxel 175 mg/m², cisplatin 50 mg/m², and carboplatin at area under the curve 5. Both treatment with prolgolimab and bevacizumab was continued until progression of disease or unacceptable toxicity.

Patients in the study were evaluated for the primary end point of overall response rate (ORR), and the secondary end points of progression-free survival (PFS), 1-year PFS, and 1-year overall survival (OS).

In terms of the primary end points, which was assessed by central radiology review per RECIST v1.1, the ORR observed with the combination of prolgolimab, bevacizumab, and chemotherapy was 63.8%. Notably, 3.5% of patients achieved complete responses (CRs) with the combination, 60.4% achieved partial responses (PRs), 10.3% had stable disease (SD), 13.8% had progressive disease (PD), and 12.1% were not evaluable for response. The disease control rate observed was 74.1%.

The median PFS per RECIST v1.1 was 8.45 months (95% CI, 5.72-10.94). Median OS in the modified intent-to-treat population was not reached, but did reach the 16-month mark for 1 patient, and exceeded 14 months for multiple patients.

Responses were also assessed per iRECIST criteria and were similar to the RECIST v1.1 results.The ORR per iRECIST was 70.7%, which included CRs in 3.5% of patients, PRs in 67.3%, SD in 10.2%, and PD in 6.9%. The DCR based on these responses was 81.0%.The median PFS per iRECIST was 13.14 months (95% CI, 8.08-13.63 months).

Treatment with prolgolimab in combination with bevacizumab and chemotherapy led to any-grade adverse events (AEs) in 98% of patients. Sixty-nine percent of the any-grade AEs that occurred were treatment-related, and these events were grade 3 or higher in 20.7% patients.

Immune-related AEs (irAEs) occurred in 37.9% of patients, of which 12.1% were grade 3 or higher. The most frequent irAEs observed during the study were grade 1 or 2 endocrine diseases (26%), and grade 2 adrenal insufficiency. The occurrence of grade 3/4 enterocolitis, grade 3 dermatitis, and grade 2/3 transaminase elevation were also significant irAEs, according to Zhukova et al.

At least 1 drug in the study combination was discontinued by 15 patients as a result of AEs. Four of these AEs were a direct result of study treatment. Discontinuation resulting from irAEs occurred in 3.45% of patients.

Further investigation of the efficacy and safety of prolgolimab in combination with bevacizumab and chemotherapy is ongoing in the phase 3, international, randomized, double-blind FERMATA study (NCT03912415), noted Zhukova et al. The study will evaluate the combination as first-line treatment for patients with advanced cervical cancer.

_REFERENCES:

_{1. Fogt S, Andabekor T, Shamsutdinova Y, et al. Final results of a phase II trial of prolgolimab with platinum-based therapy and bevacizumab in patients with advanced cervical cancer. J Clin Oncol. 2023;41(supl 16): 5536-5536. doi:10.1200/JCO.2023.41.16_suppl.5536}

_{2. Tjulandin S, Fedyanin M, Demidor L, et al. Final results of phase II trial (MIRACULUM) of the novel PD-1 inhibitor prolgolimab in patients with advanced melanoma. Ann Oncol. 2019;30(11):XI44. doi:10.1093/annonc/mdz451.027}