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Three-fourths of patients with advanced non-melanoma skin cancer of the head and neck achieved disease control with the oncolytic virus RP1 plus the PD-1 inhibitor nivolumab (Opdivo), a preliminary clinical trial showed.

The combination led to objective responses in 16 of 28 patients, including seven complete responses among 15 patients with cutaneous squamous cell carcinoma (CSCC). Responses also occurred in basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and angiosarcoma.

The most common grade ≥3 adverse event was fatigue, which occurred in five of 69 patients in the multicohort study, reported Jiaxin Niu, MD, of Banner MD Anderson Cancer Center in Gilbert, Arizona, during the Multidisciplinary Head and Neck Cancers Symposium in Phoenix.

"Tumor regression has been observed in both injected and uninjected lesions, indicative of induction of a systemic immune response," said Niu. "In cutaneous squamous cell carcinoma, a particularly high rate of complete responses has been observed. The combination of RP1 plus nivolumab has shown clear evidence of durable clinical benefit in patients with nonmelanoma skin cancer of the head and neck."

"These data further support the ongoing registration-directed clinical trial of RP1 combined with cemiplimab [Libtayo] versus cemiplimab alone in cutaneous squamous cell carcinoma, where a substantial proportion of patients would be expected to have disease of the head and neck."

A second small study reported at the symposium showed clinical benefit in 68% in a cohort of patients with progressive/recurrent squamous cell carcinoma of the head and neck (SCCHN) treated with the antibody-drug conjugate tisotumab vedotin (Tivdak). The disease control rate included five partial responses among 31 patients, reported May Cho, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Rationale and Results with RP1

By way of background, Niu pointed out that oncolytic viruses preferentially replicate in cancer cells to promote immunogenic cell death. RP1 was developed from a new strain of herpes simplex virus 1 that demonstrated potent cancer cell killing. In preclinical studies, RP1 showed enhanced antitumor activity and immunogenic cell death consistent with expression of the GALV-GP R- fusogenic glycoprotein.

Niu reported findings from the ongoing multicohort of RP1 involving patients with melanoma, nonmelanoma skin cancer, non-small cell lung cancer, and various solid tumors with microsatellite instability and mismatch repair deficiency. The report was limited to the cohort with nonmelanoma skin cancers.

The cohort consisted of 28 patients with locally advanced or metastatic cutaneous cancers of the head and neck: 15 with CSCC, four each with BCC and MCC, and five with angiosarcoma. The patients had no prior exposure to anti-PD-1/L1 therapy. The primary endpoint was best overall response.

The results showed an overall response rate of 57%, including nine responses in the 15 patients with CSCC, one each with BCC and MCC, and three patients with angiosarcoma.

Complete response in half of the CSCC subgroup "is unprecedented," said Niu.

"I was fortunate to be one of the investigators to study cemiplimab in cutaneous squamous cell carcinoma, and I can tell you from that phase II study of 60 patients, only four patients achieved complete remission, which is equivalent to 7%, so this is quite striking to us," he added.

The remaining subgroups involved few patients, but a majority of patients in each group benefited from treatment with RP1 and nivolumab. While MCC is an immunogenic tumor, the currently approved therapies for the disease have produced response rates of about 30%, as compared with 60% (three of five) in the RP1 trial, Niu noted.

All but six patients had some degree of tumor reduction with RP1 and nivolumab. Median response duration has yet to be reached, but some responses have persisted beyond 2 years, he said.

Tisotumab Vedotin Trial

Tisotumab vedotin consists of a tissue factor-directed antibody linked to a microtubule inhibitor. The agent received accelerated approval in 2021 for cervical cancer that progresses after treatment with chemotherapy. The antibody-drug conjugate exhibited activity in several tumor types known to express tissue factor, said Cho.

Investigators in the ongoing trial are evaluating single-agent tisotumab vedotin in cohorts of patients with SCCHN, non-small cell lung cancer, colorectal cancer, and pancreatic cancer. Cho reported findings from the 31-patient SCCHN cohort, a majority of whom had oropharyngeal cancer (N=16).

Patients who had received as many as three prior systemic regimens were eligible, including platinum-based chemotherapy and checkpoint inhibition (if eligible) and anti-EGFR therapy (if eligible). Assessment of human papillomavirus status was not a requirement, but 10 of 15 patients tested positive. The primary endpoint was investigator-assessed objective response.

The primary analysis showed partial responses in five (16.1%) patients and stable disease in 16 (51.6%). Median progression-free survival, a secondary endpoint, was 4.2 months; median OS was 9.4 months. Cho said that 23 of 29 (79%) evaluable patients had some degree of tumor reduction with tisotumab vedotin.

The antibody-drug conjugate was generally well tolerated, as most adverse events were grade 1/2. The most common grade 3 adverse event was anemia, which occurred in 10 patients. Six patients had grade 3 asthenia, and three each had grade 3 fatigue, dry eye, decreased appetite, hemoptysis, and conjunctivitis.

Cho said ongoing studies are evaluating tisotumab vedotin plus pembrolizumab (Keytruda) and platinum chemotherapy in patients with untreated SCCHN and as a single agent in second-line therapy.

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