Keytruda missed in liver and prostate cancer Phase 3 trials

CLINICAL AND REGULATORY

Keytruda missed in liver and prostate cancer Phase 3 trials

Merck & Co. said Keytruda pembrolizumab failed to meet its endpoints in two Phase 3 trials, one in patients with unresectable hepatocellular carcinoma and the other to treat metastatic castration-resistant prostate cancer. Overall survival and progression-free survival of HCC patients receiving Keytruda plus Lenvima lenvatinib from Eisai were not significantly improved versus Lenvima alone in the LEAP-002 study. Merck said OS in the Lenvima monotherapy arm was longer than observed in past trials. Merck and Eisai have been collaborating to develop, manufacture and commercialize Lenvima, both as monotherapy and in combination with Keytruda, since 2018. Similarly, in the KEYNOTE-921 trial, Keytruda plus docetaxel failed to significantly improve OS and PFS in patients with mCRPC. The companies said they would publish data from both studies at a forthcoming medical meeting.

Amgen heads to Phase 2 with lead bispecific antibody tarlatamab

One of the few remaining bispecific antibodies from Amgen’s BiTE platform is heading into a potentially registrational Phase 2 study after a positive efficacy readout in the challenging SCLC indication. At the World Conference on Lung Cancer, Amgen reported that tarlatamab, a bispecific T cell engager targeting DLL3 and CD3, led to an ORR of 29%, including unconfirmed responses, in 105 SCLC patients who had been treated with a median of two prior therapies. The responses included two confirmed complete and 22 confirmed partial responses. Amgen also reported that the duration of response was 13 months, with 11 patients, including the two complete responders, in ongoing response at the data cutoff. Tarlatamab led to a mOS of 13.2 months. The results are encouraging in an indication where response rates and durability are poor after relapses from initial treatment. They’re also encouraging for Amgen, which has seen little success from its BiTE platform since the 2016 approval of Blincyto blinatumomab.

Amgen’s combination strategy for Lumakras takes a blow with disappointing checkpoint inhibitor data

The future of one of the most promising KRAS inhibitor combinations is in doubt after Amgen reported disappointing results in previously treated NSCLC patients treated with Lumakras plus a checkpoint inhibitor. At the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer, Amgen presented combined data from the Phase 1b CodeBreak-100/101 studies showing its KRAS G12C inhibitor Lumakras sotorasib, plus a PD-1 inhibitor, led to a high rate of serious liver toxicity, with few measures of efficacy improved over Lumakras alone. The results are an early blow to the company’s combination strategy for Lumakras, which has led to impressive but relatively short-lived response rates in difficult-to-treat KRAS-mutant lung cancers, as resistance can develop quickly. The hope is that combinations will extend responses and increase flattening revenues.

Tislelizumab meets its primary endpoint in hepatocelullar carcinoma

Tislelizumab from BeiGene notched its eighth positive Phase 3 readout, meeting the primary endpoint of non-inferior overall survival versus sorafenib in the global Phase 3 RATIONALE 301 study to treat first-line unresectable hepatocellular carcinoma. Last month, BeiGene and partner Novartis revealed that an FDA decision on a BLA for the PD-1 inhibitor for second-line esophageal squamous cell carcinoma has been delayed due to FDA’s inability to conduct required site inspections over COVID-19-related travel restrictions in China. The PDUFA date was July 12.

AZ’s Phase 3 with Innate halted due to lack of efficacy

Shares of Innate Pharma fell 12% as AstraZeneca ended a Phase 3 study of monalizumab in metastatic squamous cell carcinoma of the head and neck after the NKG2A checkpoint inhibitor failed to meet a predefined threshold for efficacy. According to Innate, AstraZeneca’s focus is a study of the therapy in non-small cell lung cancer.

DEALS AND FINANCING

Poseida enters global collaboration with Roche focused on allogeneic CAR-T therapies

Poseida granted Roche exclusive rights and options to multiple allogeneic CAR T therapy programs, including P-BCMA-ALLO1, which is a BCMA-targeted CAR T therapy in Phase 1 testing to treat multiple myeloma; and P-CD19CD20-ALLO1, a dual-targeting CAR T against CD19 and CD20 that is expected to enter the clinic next year. Poseida will receive $110 million up front and is eligible for another $110 million in near-term milestones. In addition, the biotech is eligible for $6 billion in R&D, launch and sales milestones.