Sotorasib in KRAS G12C Mutated, Resectable, Stage Ib-IIIA NSCLC

NCT05400577 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: TH-180
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm study, conducted at two centers, of neoadjuvant sotorasib in treatment naïve patients with stage Ib-IIIa NSCLC. The study will accrue 25 patients in all. Patients must have been deemed surgically resectable and physiologically fit for surgery by a thoracic surgeon prior to enrollment.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Major pathologic response

  Major pathologic response is defined as a resection specimen with \< or = to 10% viable tumor cells in patients treated with neoadjuvant sotorasib for KRAS G12C mutated, stage Ib-IIIa NSCLC

  2 months

Secondary Outcomes (1)

• Determine the safety, feasibility and tolerability of neoadjuvant sotorasib therapy in patients with surgically resectable KRAS G12C mutant NSCLC

  1 months

Study Arms (1)

Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)

EXPERIMENTAL

Drug: Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)

Interventions

Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) DRUG

Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)

Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)

Eligibility Criteria

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

You may qualify if:

• Patients must have non-squamous NSCLC with KRAS G12C mutation identified through molecular testing (local assessment), AJCC 8 stages Ib, IIa, IIb, IIIa (single nodal station) and assessment by a thoracic surgeon that the patient is potentially resectable and physiologically operable. Lymph nodes should be pathologically staged, if feasible, prior to enrollment.
• No prior NSCLC anticancer therapy
• Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 11.0.
• Age \> 18 years.
• ECOG performance status 0 or 1
• Must have the ability to take oral medications and willing to record daily adherence to investigational product utilizing a sponsor-provided dosing diary
• Subjects must have normal organ and marrow function as defined below
• Absolute neutrophil count \> 1,000/mcL
• Platelets \> 75,000/mcL
• Total bilirubin \< 1.5 x ULN (\< 2.0 x ULN for subjects with documented Gilbert's syndrome or \< 3.0 x ULN for whom the indirect bilirubin level suggests an extrahepatic source of elevation)
• AST/ALT (SGOT/SGPT) \< 2.5 times institutional normal limits
• Creatinine clearance Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation \>=30 ml/min/1.73 m2
• Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 x ULN, OR International normalized ratio (INR) \<1.5 or within target range if on anticoagulation therapy
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document

You may not qualify if:

• Any prior therapy directed at NSCLC and Previous treatment with a direct KRAS G12C inhibitor.
• Patients receiving any other investigational agents.
• Patients with uncontrolled intercurrent illness, that would in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, informed consent, procedures, primary endpoint or study completion. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with non-invasive malignancies (e.g. in situ cervical cancer) ARE eligible.
• History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent used in this study.
• Patients receiving any medications or substances that are strong inhibitors or inducers of sotorasib ineligible. Please refer to section 5.2 for details about excluded therapies and restrictions.
• Major surgery (as assessed by treating clinician) within 28 days of study registration.
• Pregnant or breast feeding. Refer to section 4.4 for further detail.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, 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

Study Officials

• Hossein Borghaei, DO

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: June 1, 2022
• Study Start: July 13, 2022
• Primary Completion: January 1, 2024
• Study Completion: February 1, 2024
• Last Updated: July 17, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)