Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation (KRYSTAL -19)

A Phase 1/2 Trial of Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation

This study will evaluate the safety, MTD and/or RP2D, PK, and clinical activity of the combination of adagrasib with nab-sirolimus in patients with advanced solid tumors/NSCLC with a KRAS G12C mutation.

This study will evaluate the safety and tolerability and clinical activity of adagrasib in combination with nab-sirolimus in patients with advanced solid tumors harboring a KRAS G12C mutation.

The Phase 1 portion will enroll advanced solid tumors to establish the maximum tolerated dose (MTD) and/or to identify recommended Phase 2 combinatorial doses. The Phase 2 portion will enroll patients with NSCLC to further evaluate the safety/tolerability and clinical activity.

Adagrasib is an orally available small molecule inhibitor of KRAS G12C. nab-Sirolimus is a nanoparticle albumin-bound (nab) form of sirolimus, and sirolimus is an inhibitor of mechanistic target of rapamycin kinase (mTOR, previously known as mammalian target of rapamycin).

Inclusion Criteria:

• Histologically confirmed diagnosis of solid tumor malignancy (Phase 1) or NSCLC (Phase 2) with KRAS G12C mutation
• Unresectable or metastatic disease
• No available treatment with curative intent
• Adequate organ function
• Measurable disease per RECIST 1.1.

Exclusion Criteria:

• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
• History of interstitial lung disease or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease or pneumonitis
• Cardiac abnormalities