Pembrolizumab Plus Lenvatinib Elicits Clinically Meaningful Responses in Platinum-Resistant HGSOC

Pembrolizumab (Keytruda) plus lenvatinib (Lenvima) yielded clinically meaningful responses in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC), including durable partial responses (PRs) in select patients, according to findings from a phase 2, prospective, non-comparative, open-label trial (NCT05114421) presented at the 2025 SGO Annual Meeting on Women’s Cancer.1

Data from the study showed that efficacy-evaluable patients treated with the combination (n = 16) experienced an overall response rate (ORR) of 37.5% (95% CI, 15.2%-64.6%) comprised solely of PRs, and a median duration of response of 4.14 months (range, 0.67-13.1). Patients also experienced stable disease (56.25%). Additionally, 1 patient had progressive disease (6.25%), and scans showed a reduction in target lesion size from 1.2 cm to 0.5 cm which was accompanied by unequivocal progression of non-target lesions.

“Change in tumor biomarkers from baseline through the duration of the study period [were shown]. While Ca-125 and circulating tumor DNA [ctDNA] were generally correlative as seen, there were occurrences of discrepant trends as shown in [the] figures. A low initial baseline or potential inflammatory response from immunotherapy are potential contributors. Best ctDNA response was found to correlate more specifically with best response by RECIST [criteria] when discrepancy was present,” Helen D. Clark, MD, a research fellow at The University of Texas MD Anderson Cancer Center in Houston, and colleagues wrote in a poster presentation of the data.

Regarding safety, 1 patient experienced a grade 5 treatment-related adverse effect (TRAE), and 79.17% of patients had grade 3 TRAEs; no grade 4 TRAEs were reported.

Diving Into the Phase 2 Trial

The noncomparative study enrolled 24 adult patients with a histologic-confirmed diagnosis of platinum-resistant high-grade serous ovarian/peritoneal/fallopian tube cancer; resistance was defined as progression on a platinum-containing therapy or recurrence within 180 days of a prior dose of a platinum-containing regimen.2 Patients enrolled also had to have an ECOG performance score of 0 or 1.

The trial had a 3-week monotherapy phase preceding the combination therapy phase where patients were randomly assigned to receive 200 mg of intravenous pembrolizumab in cohort A and 20 mg of daily lenvatinib in cohort B.1 The combination phase of the study administered each drug at the same dose in 3-week cycles until disease progression, unacceptable toxicity, or for up to 35 cycles. Best responses were measured via RECIST 1.1 criteria among those who received at least 2 doses of pembrolizumab during the combination phase.

The first primary end point was change in the proportion of CD8-positive and CD4-positive cells that are PD1-positive CD38-positive at the monotherapy phase vs combination therapy phase of treatment.2 The second primary end point was change in the proportion of CD8-positive and CD4-positive cells that are Ki67-positive at the monotherapy phase vs combination therapy phase.

Patients enrolled were a median age of 61.5 years (range, 47.0-76.0), and most were Caucasian (91.67%), were non-Hispanic (95.83%), and had not received prior immunotherapy (87.50%).1 Patients received a median of 4.5 (range, 0.0-23.0) combination cycles and a median of 2.5 (range, 1.0-5.0) prior lines of therapy.

Clark and investigators noted the importance of the study as patients with platinum-resistant HGSOC experience low ORRs to anti–PD-1 therapies and the synergistic mechanism of action underlying the efficacy of pembrolizumab and lenvatinib is not well understood.

References

1. Clark HD, Lito K, Fellman B, et al. Efficacy of pembrolizumab and lenvatinib monotherapy and combination therapy in patients with platinum-resistant high-grade serous ovarian cancer. Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, Washington. Poster 1104.
2. Pembrolizumab and lenvatinib for the treatment of serous ovarian cancer patients. ClinicalTrials.gov. Updated January 31, 2025. Accessed March 15, 2025. https://clinicaltrials.gov/study/NCT05114421