Clinical trial NCT05840510: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor, Adult
NSCLC
Advanced Cancer
Metastatic Cancer
Malignant Neoplastic Disease
Keywords: KRAS
NSCLC
Adagrasib
KRAS G12C
mTOR
nab-sirolimus
Fyarro
ABI-009
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Aadi Bioscience, Inc.
First posted: 2023-05-03
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Safety and tolerability in the study population.
timeFrame: 30 months
measure: Phase 1: Maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D)
timeFrame: 30 months
measure: Phase 2: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase 2)
timeFrame: 30 months
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to 7 days
measure: Time to achieve maximal plasma concentration
timeFrame: Up to 1 days
measure: Maximum observed plasma concentration
timeFrame: Up to 1 days
measure: Terminal elimination half-life
timeFrame: Up to 7 days
measure: Phase 1 and 2: Evaluate efficacy endpoints characterized by overall survival, progression-free survival, and duration of response in the study population.
timeFrame: 30 months
measure: Phase 1: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
timeFrame: 30 months
measure: Phase 2: Safety and tolerability in the study population.
timeFrame: 30 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Local Institution - 019-104
state: Ohio
city: Nashville
country: United States
facility: Local Institution - 019-101
state: Tennessee
city: Houston
country: United States
facility: Local Institution - 019-102
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: