G1 Therapeutics & AstraZeneca Enter Clinical Trial Collaboration

G1 Therapeutics, Inc. recently announced a clinical trial collaboration with AstraZeneca to evaluate AstraZeneca’s epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) Tagrisso (osimertinib) in combination with G1’s oral CDK4/6 inhibitor G1T38 for the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC).

Under the terms of the agreement, G1 will sponsor and conduct a Phase 1b/2 study in collaboration with AstraZeneca in patients with NSCLC who have experienced disease progression on first-line EGFR inhibitors and harbor the EGFR T790M mutation. After defining the recommended Phase 2 dose of G1T38 in combination with Tagrisso in the Phase 1b portion, the Phase 2 study is designed to randomize 108 patients (one-to-one) to G1T38 plus Tagrisso or Tagrisso monotherapy to assess progression free survival. G1 plans to initiate the trial in the first quarter of 2018.

“CDK4/6 inhibitors can enhance the efficacy of targeted therapies, and G1T38 has already shown encouraging preclinical and initial clinical data that support a potential best-in-class profile,” said Mark Velleca, MD, PhD, Chief Executive Officer of G1 Therapeutics. “The addition of G1T38 to Tagrisso in EGFR mutation-positive non-small cell lung cancer has the potential to prolong the time to disease progression by overcoming resistance mechanisms. We look forward to collaborating with AstraZeneca to advance this compelling combination therapy to patients in need.”

“Tagrisso’s potential as a new first-line treatment of EGFR mutation-positive NSCLC has been shown in a global Phase 3 clinical trial earlier this year,” said Susan Galbraith, Head of Oncology, AstraZeneca Research and Early Development. “We are delighted to explore how Tagrisso in combination with G1T38 could provide additional benefit to patients with EGFRm non-small cell lung cancer.”

The financial terms of the non-exclusive collaboration have not been disclosed.

Tagrisso (osimertinib) is a third-generation, irreversible EGFR TKI designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, with clinical activity against central nervous system (CNS) metastases. Tagrisso 40 mg and 80 mg once-daily oral tablets have been approved in more than 60 countries, including the US, EU, Japan, and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.

G1T38 is a potential best-in-class oral CDK4/6 inhibitor being developed for use in combination with other targeted therapies in multiple oncology indications. G1T38 was well-tolerated with no grade 3/4 adverse events in a Phase 1 study of 75 healthy subjects. G1T38 is currently being evaluated in combination with Faslodex in a Phase 1b/2a study in patients with estrogen receptor-positive, HER2-negative (ER+, HER2-) breast cancer (NCT02983071). Preliminary Phase 1b data from the breast cancer study are expected to be presented at a medical meeting in the second quarter of 2018.

G1 Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the discovery and development of novel therapeutics for the treatment of cancer. G1’s two clinical assets, trilaciclib and G1T38, are CDK4/6 inhibitors, a validated and promising class of targets for anti-cancer therapeutics. Trilaciclib and G1T38 have broad therapeutic potential in many forms of cancer and may serve as the backbone of multiple combination regimens. In addition, G1 is advancing G1T48, a potential first/best-in-class oral selective estrogen receptor degrader, or SERD, which is targeted for the treatment of ER+ breast cancer. G1 is based in Research Triangle Park, N.C. For more information, please visit www.g1therapeutics.com and follow us on Twitter @G1Therapeutics.