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Two investigated doses of vibostolimab in combination with pembrolizumab resulted in comparable antitumor activity and safety in patients with locally advanced or metastatic cervical cancer who were naïve to PD-1/PD-L1 inhibitors, regardless of PD-L1 status.
Two investigated doses of vibostolimab (MK 7684a) in combination with pembrolizumab (Keytruda) resulted in comparable antitumor activity and safety in patients with locally advanced or metastatic cervical cancer who were naïve to PD-1/PD-L1 inhibitors, regardless of PD-L1 status, according to data from the phase 1 KEYVIBE-001 trial (NCT02964013) presented during the 2022 AACR Annual Meeting.1
Among all evaluable patients (n = 80), the confirmed overall response rate (ORR) achieved with the combination was 19%, which included a 9% complete response (CR) rate and a 10% partial response (PR) rate. Moreover, 24% of patients had stable disease and 46% experienced disease progression. Response data were not available for 11% of patients due to lack of post-baseline assessment or insufficient data for response assessment per RECIST v1.1 criteria.
When broken down by treatment arm, patients who received 200 mg of vibostolimab with pembrolizumab (n = 41) experienced an ORR of 15% at a median follow-up of 12 months (range, 6-23); this included a CR rate of 5%, a PR rate of 10%, and a stable disease rate of 29%. Forty-four percent of these patients experienced disease progression.
At a median follow-up of 11 months (range, 4-7), patients who received 700 mg of vibostolimab plus pembrolizumab (n = 39) experienced a higher ORR of 23%, with a CR rate of 13%, a PR rate of 10%, and a stable disease rate of 18%. In this subset, 49% of patients had progressive disease.
The median duration of response (DOR) was not reached (range, 4+ to 35+) in all patients, and in both treatment arms (range, 10 to 35+). The median progression-free survival (PFS) in the total population was 2 months (95% CI, 2-4).
“Antitumor activity was comparable between the 2 doses of vibostolimab studied, and improved response was observed irrespective of PD-L1 status compared with historic pembrolizumab monotherapy,” lead study author Ronnie Shapira-Frommer, MD, of Sheba Medical Center, and colleagues, wrote in a poster on the data.
Vibostolimab, a humanized monoclonal antibody, blocks the interaction between TIGIT and its ligands, CD155 and CD112, on tumor cells.2 In June 2018, the FDA granted pembrolizumab an accelerated approval for the treatment of patients with advanced, PD-L1–positive cervical cancer with disease progression on or after chemotherapy.3 The decision was based on data from the phase 2 KEYNOTE-158 trial (NCT02628067), in which pembrolizumab produced an ORR of 14.3% (95% CI, 7.4%-24.1%) in 77 patients with a PD-L1 combined positive score (CPS) of at least 1 who previously received at least 1 line of chemotherapy in the metastatic setting.4
KEYVIBE-001 was launched to investigate vibostolimab alone and in combination with pembrolizumab in patients with advanced solid tumors. The dose-expansion phase of the trial included patients with histologically confirmed, locally advanced, or metastatic PD-1/PD-L1 inhibitor–naïve cervical cancer who had experienced treatment failure with prior platinum-based chemotherapy.
Participants were randomized 1:1 to receive either 200 mg of vibostolimab or 700 mg of vibostolimab in combination with 200 mg of pembrolizumab every 3 weeks for up to 35 cycles. Treatment was administered until patients experienced unacceptable toxicity, disease progression, or they withdrew from the study.
The primary end points were safety and tolerability. Secondary end points included ORR, DOR, and PFS per RECIST v1.1 criteria. Safety and efficacy were assessed in patients who had received at least 1 dose of study treatment. The data cutoff date was October 6, 2021.
The median age of patients in the 700-mg cohort was 50 years (range, 32-71) vs 49 years (range, 29-76) in the 200-mg cohort. Moreover, 44% of patients had an ECOG performance status of 0 and 56% had a status of 1 in the 200-mg cohort vs 41% of patients who had an ECOG performance status of 0 and 59% who had a status of 1 in the 700-mg cohort. Additionally, 95% and 92% of patients had metastatic disease in the 200-mg and 700-mg cohorts, respectively.
In the 200-mg cohort, 49% of patients had a PD-L1 CPS of at least 1, 32% had a CPS of less than 1, and 20% had unknown status. In the 700-mg cohort, those rates were 74%, 21%, and 5%, respectively. Of those in the 200-mg cohort, 49% received 1 prior line of therapy, 37% received 2 prior lines, and 15% received 3 prior lines; these rates were 44%, 33%, and 21%, respectively, in the 700-mg cohort. Moreover, 1 patient in the 700-mg cohort previously received adjuvant or neoadjuvant treatment.
Additional data showed that when broken down by PD-L1 CPS, the confirmed ORR with the doublet was 20% in the subset of patients with a CPS of 1 or higher (n = 49); this included a CR rate of 12%, a PR rate of 8%), and a stable disease rate of 29%. Forty-one percent of patients in this subset experienced disease progression. In the subset with a PD-L1 CPS of less than 1 (n = 21), the ORR experienced with the combination was 14%, with a CR rate of 5%, a PR rate of 10%, and a stable disease rate of 14%. Fifty-seven percent of these patients experienced progressive disease.
In the 200- and 700-mg cohorts, 66% and 69% of patients, respectively, experienced treatment-related adverse effects (TRAEs) of any grade; these effects were grade 3 or 4 in 29% and 18% of patients, respectively. Moreover, serious TRAEs were experienced by 10% of those who received vibostolimab at 200 mg vs 8% of those who received the agent at 700 mg. TRAEs resulted in treatment discontinuation in 7% and 13% of patients, respectively. Notably, no TRAEs led to death in either cohort.
Common any-grade TRAEs experienced in the 200- and 700-mg cohorts, respectively, included rash (22% vs 15%), increase lipase (17% vs 13%), pruritis (17% vs 28%), diarrhea (15% vs 8%), fatigue (10% vs 15%), pyrexia (7% vs 21%), and hypothyroidism (2% vs 18%).
“Based on these data, the ongoing [phase 2] KEYVIBE-005 solid tumor basket study [NCT05007106] is evaluating the vibostolimab/pembrolizumab coformulation in PD-L1–positive [CPS of at least 1] and PD-L1–negative cancer at the recommended phase 2 dose for vibostolimab [200 mg every 3 weeks],” the study authors concluded.