Boehringer Ingelheim Enters Clinical Collaboration with Amgen to Study BI 1701963, a SOS1::pan-KRAS Inhibitor, in Combination with LUMAKRAS™ (sotorasib), a KRASG12C Inhibitor

Ingelheim, Germany – 16 September 2021 – Boehringer Ingelheim today announced a clinical phase I collaboration with Amgen to evaluate the combination of BI 1701963, the first and most advanced SOS1::pan-KRAS inhibitor exhibiting activity against a broad spectrum of KRAS alleles, and LUMAKRAS™ (sotorasib), the first US Food and Drug Administration (FDA) approved KRAS^G12C inhibitor for adult patients with locally advanced or metastatic non-small cell lung cancer. The trial will investigate potential synergistic effects of this combination, possibly improving therapeutic outcomes beyond those of KRAS^G12C inhibitor therapy alone, specifically for people living with lung and colorectal cancers. 

Preclinical data suggest that the combination of a KRAS^G12C inhibitor with a SOS1::pan-KRAS inhibitor may result in increased anti-tumor activity in KRAS G12C-driven cancers based on the complementary mechanisms of these targeted oncology agents.^1,2 By shifting the equilibrium from active KRAS towards the inactive form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C-mutant tumors to covalent KRAS^G12C inhibitors that bind to inactive KRAS. In addition, SOS1 inhibitors block feedback reactivation which occurs upon pathway inhibition.

“We are excited to partner with Amgen, who have pioneered KRAS G12C inhibition, and to further expand our program to make a difference for people living with KRAS-driven cancers,” said Francesco Di Marco, Ph.D., Corporate Senior Vice President, Global Therapy Area Head Oncology  at Boehringer Ingelheim. “Boehringer Ingelheim follows an ‘all-in’ research approach to taking cancer on, including the first and most advanced SOS1::pan-KRAS inhibitor which we investigate in several combinations and cancer types to realize even more opportunities to deliver potential therapeutic benefits to cancer patients.” 

Under the terms of the non-exclusive collaboration, Amgen will be the sponsor of the trial and Boehringer Ingelheim and Amgen will jointly share the costs of and oversee clinical development for the combined therapy. 

About BI 1701963
BI 1701963 is an investigational, orally available small molecule, that binds to the catalytic domain of SOS1 preventing the interaction with inactive KRAS. This reduces the formation of active KRAS and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers. SOS1 inhibition also simultaneously blocks feedback driven reactivation of the MAPK pathway. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type (pan-KRAS approach). SOS1::KRAS inhibitors exhibit activity on a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins, as published by Hofmann MH, et al. in Cancer Discovery, a journal of the American Association of Cancer Research (AACR). BI 1701963 is currently being evaluated in phase I clinical trials in patients with advanced KRAS-mutated cancers to evaluate safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of BI 1701963 alone and in combination with MEK inhibitors, KRAS^G12C inhibitors or irinotecan.

About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com

Boehringer Ingelheim in Oncology
Cancer takes. Takes away time. Takes away loved ones. At Boehringer Ingelheim we are giving patients new hope by taking cancer on. We are collaborating with the oncology community to deliver breakthrough treatments to patients, faster. We are committed to our focus areas of lung and gastrointestinal cancers with first-in-class treatments, and we are pursuing opportunities in other areas of high unmet need for the benefit of patients. Our commitment to innovation has already resulted in pioneering treatments, and we are advancing a unique pipeline of cancer cell directed agents, immuno-oncology therapies and combination approaches. Guided by science and unmet needs, our motivation is to transform the lives of patients and help win the fight against cancer.

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References

¹ Savarese et al., Vertical pathway inhibition with a SOS1::KRAS inhibitor enhances the efficacy of KRAS G12C inhibitors, delays feedback resistance and demonstrates durable response, 32nd EORTC-NCI-AACR Symposium, October 24-25, 2020; https://www.sciencedirect.com/science/article/pii/S0959804920311230
² Hofmann et al, Trial in Process: Phase 1 studies of BI 1701963, a SOS1::KRAS Inhibitor, in combination with MEK inhibitors, irreversible KRASG12C inhibitors or irinotecan. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT210. https://cancerres.aacrjournals.org/content/81/13_Supplement/CT210