Prolgolimab Combo Shows Antitumor Activity and Safety in Advanced Cervical Cancer

Administration of the anti–PD-1 antibody prolgolimab (BCD-100) in combination with bevacizumab (Avastin) and platinum-doublet chemotherapy resulted in high response rates and a favorable safety profile in patients with recurrent or metastatic cervical cancer, according to final results from the single-arm phase 2 CAESURA trial (NCT03912402).¹

Data presented at the 2023 ASCO Annual Meeting showed that patients treated with the prolgolimab regimen (n = 58) experienced an overall response rate (ORR) of 63.8% per RECIST v1.1 criteria; this consisted of a complete response (CR) rate of 3.5% and a partial response (PR) rate of 60.4%. Stable disease (SD) was achieved by 10.3% of patients and 13.8% experienced progressive disease (PD); 12.1% of patients were not evaluable for response. The disease control rate (DCR) was 74.1%.

Response to the combination was also assessed per iRECIST criteria and demonstrated comparable outcomes. The ORR was 70.7%, and included a 3.5% CR rate, a 67.3% PR rate, SD in 10.2% of patients, and PD in 6.9% of patients. The DCR per iRECIST criteria was 81%.

“Prolgolimab in combination with chemotherapy and bevacizumab demonstrated promising efficacy, [as well as a] known and acceptable safety profile in patients with advanced cervical cancer,” lead study author Sergey Fogt, MD, of BIOCAD, Saint-Petersburg, Russian Federation, and colleagues, wrote in a poster of the data.

The fully human monoclonal igG1 antibody, prolgolimab, is the first of its kind with an Fc-silencing LALA mutation. The antibody can block interactions between PD-1 and its ligands PD-L1 and PD-L2, leading to a reduction in tumor size.

Previously reported data from a phase 1 study (NCT03050047) showed that single-agent prolgolimab had early efficacy and acceptable safety in patients with advanced solid tumors.¹ Additionally, the agent was found to have significant antitumor activity in patients with advanced melanoma. Data from 126 patients with advanced melanoma enrolled to the phase 2 MIRACULUM study (NCT03269565) showed that 1 mg/kg of prolgolimab every 2 weeks (arm 1; n = 63) resulted in an ORR of 38.1% (95% CI, 26.4%-51.2%); those who received the agent at 3 mg/kg every 3 weeks (arm 2; n = 63) achieved an ORR of 28.6% (95% CI, 18.2%-41.5%). The 2-year progression-free survival (PFS) rates were 33.3% in arm 1 and 30.2% in arm 2; 2-year overall survival (OS) rates were 57.1% and 46.0%, respectively.²

At the 2023 ASCO Annual Meeting, investigators presented efficacy and safety data from the multicenter, open-label, single-arm, phase 2 CAESURA study, which enrolled patients 18 years of age or older with recurrent or metastatic cervical cancer.

All patients were administered a 3-mg/kg dose of prolgolimab plus 15 mg/kg of bevacizumab and platinum-based chemotherapy. The chemotherapy regimen consisted of 175 mg/m² of paclitaxel, 50 mg/m² of cisplatin, and carboplatin at area under the curve 5. Treatment with prolgolimab, bevacizumab, and chemotherapy continued for 6 cycles. This was followed by treatment with prolgolimab and bevacizumab, which continued until disease progression or intolerable toxicity. Notably, CT scans were performed at weeks 9 and 18 to monitor for suspected disease progression.

The study’s primary end point was overall response rate (ORR) as assessed by central radiology review per RECIST v1.1 criteria. Key secondary end points included PFS, 1-year PFS, and 1-year OS.

A total of 58 patients were enrolled onto the study. Regarding disease status, 72.2% had metastatic disease, 25.9% had recurrent disease, and 1.7% had persistent disease. Most patients had distant metastases (81%); 38%, 19%, and 24% of patients had 1, 2, or 3 or more organs with metastases, respectively. Additionally, 84.9% had a PD-L1 combined positive score greater than 1. Most patients (81%) had received prior therapy.

Further efficacy analysis of secondary end points revealed that the combination led to a median PFS of 8.54 months (95% CI, 5.72-10.94) per RECIST v1.1 criteria at the data cutoff date of 12 months. By iRECIST criteria, the median PFS with the regimen was 13.14 months (95% CI, 8.08-13.63). The median overall survival (OS) was not yet reached in the modified intent-to-treat population.

Safety analysis revealed that 98% of patients experienced any-grade adverse effects (AEs) with prolgolimab plus bevacizumab and chemotherapy. Of these effects, 69% were treatment-related AEs (TRAEs) and 20.7% were grade 3 or higher. Any-grade immune-related AEs (irAEs) were observed in 37.9% of patients; 12.1% of these effects were grade 3 or higher. The most common irAEs reported were grade 1 or 2 endocrine diseases (26%), and 1 case of grade 2 adrenal insufficiency. Other observed irAEs included 2 cases of grade 3/4 enterocolitis, 1 case of grade 3 dermatitis, and several cases of grade 2/3 transaminase elevation.

Treatment discontinuation due to irAEs occurred in 3.45% of patients. Fifteen patients discontinued treatment with 1 or more drugs in the study combination, 4 of which did so as a direct result of study treatment.

Data from the phase 2 CAESURA study support the ongoing investigation of prolgolimab, bevacizumab, and chemotherapy as a potential first-line option for patients with advanced cervical cancer in the phase 3, international, randomized, double-blind FERMATA study (NCT03912415).

Editor’s Note: Dr Fogt reports employment with BIOCAD.

References

1. Fogt S, Andabekov 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(suppl 16):5536. 10.1200/JCO.2023.41.16_suppl.5536
2. Tjulandin S, Demidov L, Moiseyenko V, et al. Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice. Eur J Cancer. 2021;149:222-232. doi:10.1016/j.ejca.2021.02.030