102P - Interim safety analysis of a phase 2 trial of cisplatin-sensitized radiation therapy and pembrolizumab for unresectable vulvar cancer

Background

Vulvar cancer is a rare disease with increasing incidence. Treatment can involve surgery and chemoradiation for local and regional disease, while systemic chemotherapy and immunotherapy are reserved for patients with distant metastases. Patients with unresectable or metastatic disease have relatively poor outcomes. Cisplatin and radiation (cis-RT) have been reported to have anti-tumor immunomodulatory properties in addition to their cytotoxic effects. We evaluated the addition of pembrolizumab (pembro) to cis-RT in vulvar cancer.

Methods

In this ongoing single-arm phase II trial (NCT04430699), patients with primary unresectable, incompletely resected, recurrent, or metastatic squamous cell carcinoma of the vulva undergoing RT were eligible. Patients who had received prior chemotherapy or immunotherapy were also eligible. Patients received cis 40 mg/m2 weekly concurrently with RT, and pembro 200 mg was administered every three weeks for a total of 12 cycles. The primary endpoint was ORR, and the secondary objective was 6-month RFS. Serum cytokines and HMGB-1 were assessed.

Results

At the time of the data cutoff, 15 patients were enrolled, and 14 were evaluable. Any grade adverse events (AE) occurred in all patients. Grade (G) 3 AEs occurred in 11 (78.6%) patients, most of which were related to cis. There were no G4 or higher AEs. There was one serious AE; a G3 acute kidney injury related to cis. G3 neutropenia and G3 ALT increase were observed in 4 (28.6%) and 1 (7.1%) patient respectively. The most common treatment-emergent adverse events (TEAE) were anemia (78.6%), diarrhea (78.6%), nausea (78.6%), fatigue (78.6%), and thrombocytopenia (50%). 18 AEs were related to pembro, and all were grade 1, except for G2 nephrotic syndrome in 1 patient (9%) and G2 hypothyroidism in 2 patients (14%). Patients with progressive disease were more likely to have elevated serum levels of CCL4, CCL11, and CXCL12 at cycle 3.

Conclusions

In this interim analysis, concurrent treatment with cis-RT and pembro did not lead to any unexpected AEs. Cytokine analysis might yield insight into the mechanisms of resistance. This study, the first to evaluate pembrolizumab with cis-RT, is ongoing, with a target enrollment of 24 patients.

Clinical trial identification

NCT04430699.

Legal entity responsible for the study

The authors.

Funding

Merck Sharp & Dohme Corporation.

Disclosure

O.O. Yeku: Financial Interests, Personal, Advisory Board: hC Bioscience; Financial Interests, Personal, Speaker, Consultant, Advisor: TigaTx Inc, GIMV NV; Other, Institutional, Principal Investigator: Merck Sharp & Dohme Corp, Avant Immunotherapeutics, Compugen, Ascendis Pharma A/S, ProfoundBio, Avenge Bio, Immunocore Limited, Duality Biologics; Financial Interests, Institutional, Principal Investigator: Department of Defense. S. Bouberhan: Financial Interests, Personal, Speaker, Consultant, Advisor: ImmunoGen. C.M. Castro: Financial Interests, Personal, Speaker, Consultant, Advisor: Qiagen, Teladoc, Aikili Biosystems, InfiniteMD. All other authors have declared no conflicts of interest.