Tarlox and Sotorasib in Patients With KRAS G12C Mutations

NCT05313009 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 103408
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase IB dose expansion trial with safety lead-in evaluating the safety, clinical activity/efficacy of the combination of tarloxotinib and sotorasib in patients with KRAS G12C mutation who have progressed on any small molecule targeting KRAS G12C mutant Non-Small Cell lung cancer.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response

  (OR = CR+PR) measured by CT and assessed per RECIST 1.1. Complete response (CR) and partial response (PR) require confirmatory CT

  There is no defined time frame for response assessment in the protocol. Presumably, patients are followed for response until the they stop taking study drug and/or have disease progression. The latest an assessment occurred for a patient was 40 weeks.

Secondary Outcomes (5)

• Duration of Response

  At least 4 weeks.

• Disease Control Rate

  Through study completion, an average of 18 months.

• Best Overall Response

  A minimum timeframe of 8 weeks is required for a BOR of SD.

• Progression Free Survival

  From the date of first study drug dose to the date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 100 months.

• Overall Survival

  Follow-up for survival continues until 6 months after the last patient on-study visit.

Study Arms (2)

STAGE 1: SAFETY LEAD IN (n=6-18, depending on number of DLs explored)

EXPERIMENTAL

SAFETY LEAD IN (n=6-18, depending on number of DLs explored) 3+3 design dependent on DLTs

Drug: Sotorasib and Tarloxotinib

STAGE 2: EFFICACY (n=12)

EXPERIMENTAL

EFFICACY (n=12)

Drug: Sotorasib and Tarloxotinib

Interventions

Sotorasib and Tarloxotinib DRUG

Sotorasib 960 mg PO daily + tarloxotinib 150 mg/m2 IV weekly

STAGE 1: SAFETY LEAD IN (n=6-18, depending on number of DLs explored); STAGE 2: EFFICACY (n=12)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of squamous or non-squamous NSCLC with KRAS G12C mutation
• Unresectable or metastatic disease
• No available treatment with curative intent
• Must have previously received treatment with at least a platinum-containing chemotherapy regimen
• Must have previously received at least one month trial of sotorasib or a therapy targeting KRAS G12C mutation with documented progression. If sotorasib dose from prior therapy was reduced for toxicity, patients that meet the above criteria are expected to receive study treatment at the reduced dose.
• Must have measurable or evaluable disease as defined by RECIST 1.1
• Age \>18 years
• Life expectancy of at least 3 months
• Recovery from adverse effect of prior therapy at the time of enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Laboratory values within the screening period:
• Absolute neutrophile count \> 1000/mm3
• Platelet count \> 100,000 /mm3
• Hemoglobin \> 8 in the absence of transfusions for at least 2 weeks
• Total bilirubin \< 1.5 x upper limit of normal (or \< 3 x ULN if associated with liver metastases or Gilbert's disease)

You may not qualify if:

• Active brain metastases. Patients are eligible if brain metastases are asymptomatic measuring no more than 2.0 cm each and confined to the cerebral hemispheres if neurologically stable and must be on a stable or tapering dose of corticosteroids for at least 2 weeks prior to C1D1.
• History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow pills
• Congestive heart failure \> NYHA Class 3
• QTc \> 480 milliseconds or family history of Long QT syndrome
• Ongoing need for a medication with a known risk of Torsades de Pointes that cannot be switched to alternative treatment prior to study entry.
• Pregnancy or breast feeding
• Has known activating oncogene-driver mutations, including but not limited to KRAS, ALK, ROS1, RET, BRAF, NTRK1/2/3, MET, EGFR
• Previously have received anti-EGFR or anti-HER2 TKIs
• Previously have received anti-EGFR or anti-HER2 monoclonal antibodies
• Clinically active or symptomatic interstitial lung disease
• AST and ALT\>3xULN if no hepatic metastases are present; \>5xULN if hepatic metastases are present; total bilirubin \>1.5xULN; 3xULN with direct bilirubin \>1.5 x ULN in the presence of Gilbert's syndrome
• Known concurrently malignancy that is expected to require active treatment within 2 years or may interfere with the interpretation of the efficacy and safety outcomes of this study.
• Infection requiring systemic treatment within 7 days prior to cycle 1 day1.

Sponsors & Collaborators

• Rain Oncology Inc: collaborator
• Medical University of South Carolina: lead

Study Sites (1)

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sotorasib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

1 participant died prior to first dose of study drug due to existing comorbidity complications and was non-evaluable. Study was prematurely terminated due to study drug being withdrawn by manufacturer. Overall survival calculation influenced by one participant that withdrew consent for follow-up at the time of end of study treatment and admission to hospice care.

Results Point of Contact

• Title: Alan Brisendine
• Organization: Medical University of South Carolina

brisend@musc.edu

843-792-9007

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: (1) Safety lead-in: A minimum of 6 patients and as many as 18 patients will be enrolled in a safety lead-in cohort to evaluate the safety of the combination of tarloxotinib and sotorasib. (2) Dose expansion: Once the tarloxotinib RP2Dc is reached, an expansion cohort of up to 12 patients will be enrolled to evaluate the safety of the combination of tarloxotinib and sotorasib.

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: April 6, 2022
• Study Start: March 7, 2022
• Primary Completion: July 7, 2023
• Study Completion: December 31, 2023
• Last Updated: December 16, 2025
• Results First Posted: December 16, 2025

Record last verified: 2025-11

Locations

US (1)