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The combination of pembrolizumab and lenvatinib showed promising activity including durable responses in patients with 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.
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.
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