A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis

NCT05180422 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 02AT21-KRAS
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, non-randomized, open-label, phase I/II study to evaluate the safety and tolerability of AMG 510 plus MVASI in subjects with advanced KRAS p.G12C mutant non-small cell lung cancer (NSCLC) with small, untreated brain metastases.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Dose Exploration

  To determine the feasibility and safety of AMG 510 in combination with MVASI for the treatment of patients with KRAS G12C mutant NSCLC with asymptomatic, untreated brain metastases. For patients enrolled in the dose exploration part of the study (anticipated to be the initial 9-18 patients participating in the study), whose participation will establish the recommended phase 2 dose (RP2D), dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) required for 21 days after initiating protocol-indicated treatment. Satisfactory completion of the physical exam and safety labs is required to help detect evidence of past or present DLT as having occurred during the first 21 days of protocol-indicated treatment.

  21 days

• Dose Expansion

  To determine the CNS objective response and rate of salvage radiation to the CNS 18 weeks after therapy initiation. The CNS objective response rate using Rando-BM will be evaluated at 18 weeks. Whether or not the patient requires salvage radiation therapy will be evaluated at 18 weeks

  18 weeks

• Dose Exploration

  Safety and tolerability (phase I component). Dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) is required for 21 days after initiating protocol-indicated treatment A minimum of 6 patients will be treated at the Maximum tolerated dose on the phase I portion of the study in order to obtain sufficient toxicity data prior to proceeding to the phase II evaluation of this regimen

  21 days

• Dose Expansion

  CNS objective response, assessed using RANO-BM.

  18 weeks

• Dose Expansion

  Initiation of salvage radiation therapy to the CNS at 18 weeks (phase II component).

  18 weeks

Secondary Outcomes (4)

• Dose Expansion

  18.5 months

• Dose Expansion

  18 weeks

• Dose Expansion

  18.5 months

• Dose Expansion

  18.5 months

Study Arms (1)

Dose Expansion

EXPERIMENTAL

AMG 510/MVASI

Drug: AMG 510; Drug: MVASI

Interventions

AMG 510 DRUG

Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food.

Dose Expansion

MVASI DRUG

Intravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle).

Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Signed and dated written informed consent.
• Male or female ≥ 18 years of age at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• As estimated by study physician, life expectancy ≥ 12 weeks.
• Histologically proven, locally advanced, recurrent or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC), with pathological documentation of KRAS p.G12C mutation identified through DNA sequencing either in tumor tissue or blood circulating tumor DNA.
• At least one untreated brain metastasis ≥ 5mm in diameter in any line of treatment:
• Subjects with largest measurable intracranial lesion ≥5 mm but \<10 mm may be allowed to enroll upon agreement with investigator (for patients with target lesions of ≥ 5mm but \<10 mm, 1.5 mm slice thickness brain MRI is required).
• "Untreated" refers to the lesion not being previously treated with stereotactic radiosurgery (SRS).
• Prior treatment with whole brain radiation therapy or local surgery is permissible provided unequivocal progression in the lesion has since occurred and completion 14 days prior to study enrollment.
• For at least 7 days prior to first dose of AMG 510 and MVASI in this study: Patient must be asymptomatic from CNS metastases and on a stable dose of corticosteroids.
• Able to take oral medications and willing to record daily adherence to investigational product.
• As assessed by electrocardiogram (ECG) completed ≤ 14 days before initiation of protocol treatment, the corrected QT interval (QTc) will be calculated by Fridericia's method (QTcF) - see Section 7.12. Eligible candidates (male or female) must have the following QTcF value on baseline ECG:
• QTcF ≤ 470 ms.
• The average QTcF value from three (3) separate ECG tracings, each performed on the same day (ideally at least 5 minutes apart), will serve as the baseline QTcF value used to meet eligibility.
• Adequate organ and bone marrow function resulted ≤ 14 days prior to first dose of protocol-indicated treatment:

You may not qualify if:

• Patients meeting any of the following criteria will not be permitted to enter the trial:
• Other coexisting malignancies or malignancies diagnosed within the previous 2 years are not eligible.
• Exceptions to this include non-melanoma skin cancer, cervical cancer in-situ, well-differentiated thyroid cancer or prostate cancer.
• Other cancers that per assessment of the principal investigator are not prognosis-limiting can be allowed after review by the principal investigator. If there is no evidence of disease for at least 3 years prior to initiating treatment in this study, patients may be eligible.
• Prior receipt of AMG-510, other KRAS G12C inhibitors, or VEGF inhibitors for the treatment of non-small cell lung cancer.
• Myocardial infarction within 6 months of study Day 1, symptomatic congestive heart failure equivalent to New York Heart Association \> Class II (see Appendix 2) or unstable (requiring hospitalization or heart catheterization) angina currently.
• Patient on full dose, therapeutic anticoagulation for thromboembolic event, arrhythmia, or prothesis with coumadin.
• Evidence of clinically significant hemorrhage (per study physician) in untreated CNS lesion(s) on screening MRI.
• Major surgery within 28 days of enrollment or presence of a non-healing wound.
• Proteinuria of greater than 1 gram per 24 hours.
• Recent history of moderate or severe hemoptysis within 7 days (greater than 20mL of pure blood within 24 hours).

Sponsors & Collaborators

• Criterium, Inc.: lead
• Amgen: collaborator

Study Sites (1)

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sotorasib; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Wade Iams, MD, MSCI

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 6, 2021
• First Posted: January 6, 2022
• Study Start: June 15, 2022
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)