On April 1, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported that preclinical data for SRA737+LDG, its Chk1 inhibitor plus non-cytotoxic low dose gemcitabine (LDG), in combination with immunotherapy, are being reported today in a late-breaking oral presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held in Atlanta, Georgia (Press release, Sierra Oncology, APR 1, 2019, View Source [SID1234534861]).

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"Given the limited response rates for anti-PD-L1 drugs in patients with small cell lung cancer (SCLC), better treatment options are sorely needed. Our data, showing durable tumor regressions when combining SRA737+LDG with anti-PD-L1 in a mouse model, warrant further clinical studies to investigate the potential of this approach as a strategy to improve outcomes in our patients," said senior researcher Lauren Averett Byers, M.D., Associate Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, Texas.

In the study, SRA737+LDG demonstrated significant anti-tumor activity when combined with anti-PD-L1 in a mouse model of SCLC, resulting in durable tumor regressions. These results were accompanied by an induction of anti-tumor cytotoxic T-cells and M1 macrophages and a corresponding reduction in several pro-tumorigenic cell types in the tumors of drug-treated animals.

"The unique replication stress-inducing properties of SRA737 as potentiated by non-cytotoxic low dose gemcitabine have been previously demonstrated to result in intrinsic anti-tumor activity in multiple preclinical models. These striking new data provide evidence for SRA737+LDG’s activation of innate immune signaling and the establishment of an anti-tumor immune microenvironment that synergizes with immune checkpoint inhibitors," said Dr. Christian Hassig, Chief Scientific Officer, Sierra Oncology. "These findings provide a mechanistic basis for the growing body of evidence highlighting a synergistic interplay between replication stress and anti-tumor immune responses and afford a compelling rationale for evaluating SRA737+LDG with immunotherapy in the clinic."

SRA737 AACR (Free AACR Whitepaper) Late-Breaking Oral Presentation:
Date/Time: Monday, April 1st from 3:00 to 5:00 pm ET
Session: Minisymposium: Late-Breaking Research 2
Title: Combination treatment of the CHK1 inhibitor, SRA737, and low dose gemcitabine demonstrates profound synergy with anti-PD-L1 inducing durable tumor regressions and modulating the immune microenvironment in small cell lung cancer
Authors: Triparna Sen, Carminia M. Della Corte, Snezana Milutinovic, Lixia Diao, Robert J Cardnell, Ryan J. Hansen, Bryan Strouse, Michael P. Hedrick, Christian Hassig, Jing Wang, Lauren A Byers.
Location: Georgia World Congress Center, Room B404

Summary slides from this presentation will be made available on the company’s website at www.sierraoncology.com

About SRA737+LDG
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine acts as a potent inducer of replication stress that potentiates SRA737’s anti-tumor activity.

Phase 1/2 clinical trials of SRA737 as monotherapy (NCT02797964) and in combination with low dose gemcitabine (NCT02797977) in multiple solid tumors (ovarian, prostate, non-small cell lung, squamous (head & neck, anal), colorectal, small cell lung, sarcoma, cervical, anogenital) are ongoing. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor.

Sierra Oncology retains the global commercialization rights to SRA737.