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#ESMO24: Incyte gears up to face FDA once again with more Zynyz data in rare anal cancer

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BARCELONA — Incyte said it has positive late-phase results for its PD-1 drug Zynyz in certain patients with squamous cell carcinoma, three years after the FDA asked for more data.

The Phase 3 POD1UM-303 trial of Zynyz plus chemotherapy in inoperable, locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) met its primary endpoint, with the treatment hitting 9.3-month progression-free survival versus 7.39 months for chemotherapy plus placebo (p=0.0006).

There was also a “strong trend” toward improved survival with the treatment, although the data were still immature, according to results presented on Saturday at the European Society for Medical Oncology annual meeting in Barcelona. The addition of Zynyz to chemotherapy was also safe, with no new safety signals observed, according to Incyte.

Incyte filed for approval for Zynyz in January 2021 in these same patients with results from a single-armed Phase 2 trial under the priority review pathway. But the FDA handed the company a CRL in July that year in which the agency sought “additional data” on the drug’s clinical benefit.

In 2023, Zynyz secured an FDA approval elsewhere, in patients with metastatic or recurrent locally advanced merkel cell carcinoma.

The overall response rate was a point of contention during Incyte’s first attempt in SCAC, with Zynyz showing 14% ORR among 94 patients in the single-armed trial. Data from the new placebo-controlled Phase 3 study that enrolled 308 participants show the treatment arm hit a 55.8% ORR versus 44.2% for chemo with placebo, good for a statistically significant p-value of 0.0129.

Incyte plans to file the drug again with the FDA in SCAC by the end of the year with a potential launch in the fall next year, CEO Hervé Hoppenot told Endpoints News in an interview ahead of the confab.

Zynyz is the only PD-1 to be studied in chemotherapy-naïve SCAC patients to date, Hoppenot added.

But the company is not expecting Zynyz to be a multibillion-dollar opportunity. The market size for this disease in this setting “is relatively limited,” Hoppenot said. Rather, Zynyz is envisioned to unlock the “optionality for doing clinical trials in combination with the rest of our pipeline for the future,” on top of contributing to its revenue in the short term, he added.

Another noteworthy asset in the biotech’s pipeline includes a small molecule CDK2 inhibitor dubbed INCB123667, which is in clinical proof-of-concept studies for solid tumors.

In July, Incyte dropped four early-stage drug candidates in a response to an “evolving treatment landscape” and the “evolution” of its internal pipeline. These comprised two oral small molecule PD-L1 inhibitors, a TIM-3 monoclonal antibody and a LAG-3xPD-1 bispecific.

SCAC, which accounts for 3% of all digestive system cancers, is linked with human papillomavirus and HIV infections, Incyte said.


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