NEW YORK – Blueprint Medicines on Friday announced a clinical trial collaboration with AstraZeneca to study its EGFR inhibitors BLU-945 and BLU-701 in combination with AstraZeneca's Tagrisso (osimertinib) in non-small cell lung cancer.
Blueprint will begin a trial cohort in its ongoing Phase I/II SYMPHONY trial to assess BLU-945 in combination with Tagrisso in patients with second-line or later EGFR-mutant NSCLC whose disease has progressed after prior treatment with Tagrisso.
Blueprint initiated the combination cohort after reporting positive initial data from the BLU-945 monotherapy regimen. The drug showed dose-dependent decreases of EGFR variant allele fractions in circulating tumor DNA and anti-tumor activity, including one partial response.
The SYMPHONY trial began last year evaluating BLU-945 as a monotherapy to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and anticancer activity of the drug. This second stage of the study will determine the recommended Phase II combination dose regimen.
By the end of this year, the company is also planning a potentially registrational expansion cohort in biomarker-selected second-line patients, and an expansion cohort in front-line NSCLC patients. Blueprint is also hoping to explore combinations of BLU-945 with BLU-701, chemotherapy, and antibody-drug conjugate therapy in the future.
"We believe BLU-945 is distinguished from other EGFR-directed therapies, based on its ability to inhibit the most difficult-to-target EGFR mutations while maintaining a wide therapeutic index over wild-type EGFR, a known driver of toxicity," Fouad Namouni, president of research and development at Blueprint Medicines, said in a statement. "As a result, BLU-945 has significant potential as a combination partner with other targeted therapies and broad-acting agents."
Along with BLU-945, Blueprint is also planning to study its other EGFR inhibitor, BLU-701, with Tagrisso in the ongoing Phase I/II HARMONY trial in patients with EGFR-mutant NSCLC. Under the agreement, AstraZeneca will provide Tagrisso for both the SYMPHONY and HARMONY clinical trials.
Last year, Blueprint licensed both EGFR inhibitors to Zai Lab in a $615 million deal for development and commercialization in greater China.