Portage Biotech Inc. announced that it has entered into an agreement with Merck. The collaboration will evaluate Portage's lead invariant natural killer T cell agonist, PORT-2, in combination with KEYTRUDA Merck's anti-PD-1 therapy, for patients with front-line as well as PD-1 refractory non-small cell lung cancer. Under the terms of the agreement, Merck will be providing KEYTRUDA for Portage Biotech's IMPORT-201 trial, a Phase 1/2 study of PORT-2 for patients with NSCLC and advanced melanoma.

The two companies will establish a Joint Development Committee to optimally evaluate the study's combination arms. PORT-2 is an iNKT agonist packaged in a liposome and is designed to activate both the innate and adaptive immune systems and inhibit negative signals in the tumor microenvironment. Preclinical data have shown that PORT-2 increases expression of PD-L1 on cancer cells. Additionally, PORT-2 demonstrated single agent activity in PD-1 resistant animal tumor models, and the combination of PORT-2 plus an anti-PD-1 antibody restored sensitivity to anti-PD-1 therapy in these models.

As reported at the 2022 American Society of Clinical Oncology conference, early clinical data suggests that PORT-2 is well tolerated and active as a monotherapy. Portage's unique four arm Phase 2 trial, IMPORT-201, will seek to evaluate PORT-2 in multiple settings with unmet medical need: Randomized cohort: Patients with first-line PD-L1 positive NSCLC will be randomized to receive KEYTRUDA alone or in combination with PORT-2. Those patients in the KEYTRUDA group will be offered the opportunity to cross over at progression to determine whether PORT-2 will resensitize them to checkpoint inhibition. NSCLC proof of concept: Patients with PD-L1 negative NSCLC will undergo biopsy before and after one dose of PORT-2 to evaluate if PORT-2 increases PD-L1 expression, followed by treatment with PORT-2 in combination with KEYTRUDA.

Melanoma proof of concept: Patients with immunotherapy-refractory melanoma will be treated with PORT-2 monotherapy.