Merck, Amgen Begin Combo Immunotherapy Trial In Melanoma

Merck and its partner Amgen announced the initiation of the clinical trial investigating the combination immunotherapy of Amgen’s talimogene laherparepvec with Merck’s anti-PD-1 therapy, Keytruda (pembrolizumab), in patients with regionally or distantly metastatic melanoma.

Talimogene laherparepvec is an investigational oncolytic immunotherapy which selectively replicates in tumors, but not in normal tissue to trigger an immune response against metastasized cancer cells. Amgen has filed a Biologics License Application with the U.S. Food and Drug Administration (FDA) as well as a Marketing Authorization Application in the EU for the drug as treatment for patients with regionally or distantly metastatic melanoma.

Keytruda is an FDA-approved monoclonal antibody (mAb) that inhibits PD-1 from interacting with its ligands PD-L1 and PD-L2. Pembrolizumab received its second breakthrough therapy designation in the U.S. in October. The drug is also being studied as treatment for relapsed/refractory classical Hodgkin Lymphoma (cHL) as well as in other indications.

The two drugs will be studied in a multicenter, open label clinical trial for their efficacy as a combination treatment compared to Keytruda alone and following progression after monotherapy with Keytruda. The trial will also assess the safety of talimogene laherparepvec in combination with pembrolizumab.

F. Stephen Hodi, director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute and Steering Committee Chair for the study, said, “Talimogene laherparepvec is designed to promote tumor antigen release and presentation to initiate an anti-tumor immune response, which may be complementary to Keytruda's role in releasing PD-1 pathway-mediated inhibition of anti-tumor immune responses. Antigen release and presentation is a fundamental step required for mounting a systemic effect against melanoma, and we think there is a strong rationale for combining the oncolytic immunotherapy talimogene laherparepvec with the immune checkpoint inhibitor Keytruda.”

The study is designed to progress through two phases. The first phase will investigate the combo immunotherapy in patients with untreated, unresected, stage IIIB to IVM1c melanoma. The second part will be randomized to further investigate the safety and efficacy of the combination treatment. The trial has enrolled its first patients and will involve an estimated 110 patients across 35 clinical study centers in the U.S., EU, and Australia.

Dr. Eric Rubin, VP of clinical development for oncology, Merck Research Laboratories, said, “Merck is advancing the study of immuno-oncology combinations with Keytruda across a broad range of malignancies. We are pleased to collaborate with Amgen to evaluate the potential of Keytruda and talimogene laherparepvec as a combination regimen for the treatment of advanced melanoma.”