G1 Therapeutics Announces Initiation of Phase 1b/2 Clinical Trial of G1T38 in Combination with Tagrisso for EGFR-Mutant Non-Small Cell Lung Cancer

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RESEARCH TRIANGLE PARK, N.C., April 16, 2018 (GLOBE NEWSWIRE) — G1 Therapeutics, Inc. (Nasdaq:GTHX), a clinical-stage oncology company, today announced that it has initiated a Phase 1b/2 clinical trial assessing G1T38, its oral CDK4/6 inhibitor, in combination with Tagrisso® (osimertinib) in people with EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC). AstraZeneca (LON: AZN) is providing Tagrisso for this trial under a non-exclusive clinical trial collaboration agreement.

“G1T38 inhibits tumor cell growth, providing a rationale for combining it with other targeted therapies, including EGFR-TKI inhibitors such as Tagrisso. In a prior Phase 1a trial, G1T38 had no dose-limiting toxicities and was well tolerated with no impact on liver or cardiovascular function, presenting evidence of a favorable safety and tolerability profile for combination therapy,” said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D of G1 Therapeutics. “Despite advances in care, lung cancer remains the leading cause of cancer death globally. Non-small cell lung cancer represents the majority of lung cancers, and there is a significant need for new treatment options that improve outcomes for people with this disease.”

The open-label trial is expected to enroll approximately 145 participants in two parts: a safety, pharmacokinetic and dose-finding portion (Part 1); and a subsequent randomized portion (Part 2). Primary outcome measures include safety and tolerability, identifying a recommended Phase 2 dose and progression-free survival (PFS). Secondary outcome measures include assessment of pharmacokinetics, tumor response and overall survival (OS).

“There is a growing body of evidence that CDK4/6 inhibitor combination regimens can be effective in a range of tumor types. In addition to this trial in lung cancer, we are conducting a trial of G1T38 in combination with Faslodex in people with ER+, HER2- breast cancer. Preliminary Phase 1b data from that trial will be presented in the second quarter,” said Mark Velleca, M.D., Ph.D., Chief Executive Officer of G1 Therapeutics. “We are excited about G1T38’s best-in-class potential and believe that it could be backbone therapy for combination regimens across multiple solid and hematological malignancies.”

About Lung Cancer and Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death globally among both men and women, more than breast, prostate and colorectal cancers combined1. Lung cancer is the second most common cancer in both men and women in the U.S., with 14 percent of new cancers being lung cancers. The American Cancer Society estimates that in the U.S. alone there will be approximately 235,000 new cases of lung cancer and 155,000 deaths from lung cancer in 20182.

Approximately 80-85 percent of all lung cancers are NSCLC3; 10-15 percent of patients in the U.S. and Europe4, and 30-40 percent of patients in Asia5, have EGFRm NSCLC.

About G1T38
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. Preclinical data presented at the American Association for Cancer Research 2016 Annual Meeting and published in Molecular Cancer Research and Oncotarget demonstrated the compound’s differentiation from other CDK4/6 inhibitors.

G1T38 is currently being evaluated in two Phase 1/2 clinical trials: a trial in combination with Faslodex® for people with estrogen receptor-positive, HER2-negative breast cancer (NCT02983071), and a trial in combination with Tagrisso® for people with EGFRm non-small cell lung cancer (NCT03455829).

About Tagrisso
Tagrisso, developed and commercialized by AstraZeneca, 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 received Accelerated Approval for EGFR T790M mutation-positive advanced non-small cell lung cancer (NSCLC) in 2015 and full approval in 2017. The U.S. Food and Drug Administration is currently reviewing Tagrisso as a 1st-line treatment for EGFRm NSCLC under Priority Review.

About Faslodex
Faslodex, developed and commercialized by AstraZeneca, represents a hormonal treatment approach that helps to slow tumor growth by blocking and degrading the estrogen receptor – a key driver of disease progression. Faslodex is indicated for the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy. Faslodex has also been licensed for use with CDK4/6 inhibitors, palbociclib (in the U.S., EU and several other markets) and abemaciclib (in the U.S. only) for the treatment of women with ER+ / HER2- advanced breast cancer, whose cancer has progressed after endocrine therapy. In Japan, Faslodex is also approved for use in combination with any CDK4/6 inhibitor.

About G1 Therapeutics
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, NC. For additional information, please visit www.g1therapeutics.com and follow us on Twitter @G1Therapeutics.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this news release include, but are not limited to, the therapeutic potential of trilaciclib, G1T38 and G1T48, and are based on G1 Therapeutics’ expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause G1 Therapeutics’ actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in G1 Therapeutics’ filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections contained therein and include, but are not limited to, the inherent uncertainties associated with developing new products or technologies and operating as a development-stage company; G1 Therapeutics’ ability to complete clinical trials for, obtain approvals for and commercialize any of its product candidates; G1 Therapeutics’ ability to recruit and enroll patients in its studies; competition in the industry in which G1 Therapeutics operates; and market conditions. Except as required by law, G1 Therapeutics assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Jeff Macdonald
Head of Investor Relations / Public Relations

1 World Health Organization 2018: http://www.who.int/mediacentre/factsheets/fs297/en/

2 American Cancer Society: https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html

3 American Cancer Society: https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html

4 Journal of Clinical Oncology: J Clin Oncol 29:2121-2127; International Journal of Clinical and Experimental Pathology:
Int J Clin Exp Pathol 2013;6(12):2800-2812.

5 Journal of Clinical Pathology: J Clin Pathol 2013;66:79–89.