A Phase I Study of Adagrasib and Durvalumab for Treatment of Advanced Non-small Cell Lung Cancers and Gastro-intestinal Cancers Harboring KRAS G12C Mutations

NCT05848843 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0782NCI-2023-03640
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To find a recommended dose of the combination of adagrasib and durvalumab that can be given to patients with cancers that have a KRAS G12C mutation.

Conditions

Lung Cancer; Gastro-intestinal Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (2)

Dose Confirmation Cohort

EXPERIMENTAL

Drug: Durvalumab; Drug: Adagrasib

Dose Expansion Cohort

EXPERIMENTAL

Drug: Durvalumab; Drug: Adagrasib

Interventions

Durvalumab DRUG

Given by vein (IV)

Dose Confirmation Cohort; Dose Expansion Cohort

Adagrasib DRUG

Given by PO

Dose Confirmation Cohort; Dose Expansion Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For the dose confirmation cohort, histologically confirmed diagnosis of NSCLC or carcinomas of gastro-intestinal tract, including, but not limited to, colorectal adenocarcinoma, pancreatic adenocarcinoma, and cholangiocarcinoma. For the Dose Expansion cohorts, only NSCLC and colorectal adenocarcinoma histologies are eligible.
• Presence of KRAS G12C mutation detected by assay performed in a CLIA-certified environment.
• Metastatic disease or locally advanced disease not amenable to local therapy.
• ECOG performance status 0 or 1.
• Presence of measurable disease per RECIST v1.1.
• Any number of prior lines of therapy, including prior KRAS G12C inhibitor. For the Dose Expansion cohorts, only treatment naïve NSCLC patients and colorectal adenocarcinoma patients with disease progression on prior KRAS G12Ci are eligible. NSCLC patients that completed curative intent treatment of their disease ≥6 months prior to enrollment are eligible for frontline expansion cohort as long as they have not been previously treated with a KRAS G12C inhibitor.
• Age ≥ 18 years.
• Life expectancy of at least 3 months.
• Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) and radiation therapy discontinued at least 2 weeks before first dose date.
• Recovery from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia and parameters superseded by other eligibility criteria \[eg, laboratory parameters\]).
• Laboratory values within the screening period:
• Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0 x 109/L)
• Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) (if associated with liver metastases or Gilbert's disease, ≤ 3 x ULN)

You may not qualify if:

• Radiation to the lung \>30 Gy within 3 months prior to the first dose of study treatment.
• Active brain metastases. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to the first dose of study treatment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• Carcinomatous meningitis.
• History of significant hemoptysis or hemorrhage within 4 weeks of the first dose date.
• Active or prior documented autoimmune or inflammatory disease, as follows:
• Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of interstitial lung disease (ILD) or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD or pneumonitis.
• Other medically important autoimmune disease within 2 years prior to the first dose of study treatment. NOTE: Patients with Type 1 diabetes, vitiligo, Graves' disease requiring only hormone replacement, hypothyroidism, or psoriasis not requiring systemic treatment within the past 2 years are not excluded.
• Immunocompromising conditions, as follows:
• Use of immunosuppressive medication within 28 days prior to the first dose of study treatment, with the exceptions of corticosteroids.
• History of primary immunodeficiency.
• History of allogeneic transplant.
• Receipt of a live vaccine within 30 days prior to first dose of study treatment.
• Known severe hypersensitivity to study drugs and/or any of its excipients.
• Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or C infection. Patients treated for hepatitis C with no detectable viral load are permitted.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• AstraZeneca: collaborator
• Mirati Therapeutics Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

durvalumab; adagrasib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Marcelo V. Negrao, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 8, 2023
• Study Start: April 25, 2023
• Primary Completion: January 16, 2024
• Study Completion: January 16, 2024
• Last Updated: January 23, 2024

Record last verified: 2024-01

Locations

US (1)