Merck and Nectin to Study Novel Anti-PVR Candidate with Keytruda

Merck_Kena Betancur/Getty Images

Courtesy of Kena Betancur/Getty Images

Merck and New Jersey-based Nectin Therapeutics announced a research collaboration agreement Tuesday to study the safety and efficacy of Nectin’s investigational antibody NTX1088 in locally advanced and metastatic solid tumors.

The research partnership will pair NTX1088 with Merck’s PD-1 inhibitor, Keytruda (pembrolizumab). Nectin will be responsible for the study’s overall operations, while Merck will supply Keytruda for the patients.

Nectin and Merck kicked off the Phase I KEYNOTE-E92 study in November 2022, assessing NTX1088 as a monotherapy and a combo with Keytruda. The trial consists of a Phase Ia dose-escalation part to evaluate the candidate’s safety and tolerability and to determine a Phase II dose.

KEYNOTE-E92 also includes a Phase Ib dose-expansion part to study NTX1088’s safety and tolerability further and conduct exploratory efficacy assessments.

Fabian Tenenbaum_Nectin Therapeutics
Fabian Tenenbaum

The partners expect to start evaluating biomarker data toward the end of this year and into 2024, Fabian Tenenbaum, CEO, Nectin, told BioSpace in a statement.

KEYNOTE-E92’s Phase Ia component is set to end in 2024, while the Phase Ib is scheduled to begin in mid-2024 in a selected patient or tumor population.

Nectin also continues to enhance its capabilities to design a better later-stage clinical and regulatory development strategy, Tenenbaum said.

Targeting a Novel Pathway

NTX1088, the molecule at the center of Tuesday’s research collaboration, is a first-in-class investigational monoclonal antibody that targets PVR, a transmembrane protein commonly found on cancer cells that have developed resistance to PD1 and PD-L1 immune checkpoint inhibitors.

“PVR expression could represent a critical escape mechanism in many types of prevalent and difficult-to-treat cancers,” Tenenbaum said. This could explain why, despite all the progress in immuno-oncology, some 80% of patients fail to achieve a durable response to approved treatments.

This mechanism of action makes NTX1088 the first and so far, only treatment approach that seeks to restore the activity of DNAM1, a glycoprotein essential for the function of T and natural killer cells, which PVR suppresses on cancer cells.

In preclinical studies, Nectin found that blocking PVR with NTX1088 leads to robust immune activation and anti-cancer activity – even in models that are refractive to PD(L)1 treatments. The company’s experiments have also shown good progress between PVR and PD1 blockade, pointing to the potential of combination treatments.

Aside from NTX1088, Nectin is advancing four other candidates within the nectin family of proteins, which are either first-in-class or have best-in-class potential. 

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