A Phase II Study of Neoadjuvant Sotorasib in Combination With Cisplatin or Carboplatin and Pemetrexed for Surgically Resectable Stage IIA-IIIB Non-Squamous Non-Small Cell Lung Cancer With a KRAS p.G12C Mutation

NCT05118854 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0649NCI-2021-10907
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II, single-arm, open-label study evaluating the efficacy, safety and tolerability of neoadjuvant sotorasib in combination with cisplatin (or carboplatin) and pemetrexed chemotherapy for patients with surgically resectable stage IIA - IIIB (T3-T4/N2) (based on AJCC 8th edition), non-squamous NSCLC with a KRAS p.G12C mutation. The primary objective of the study is to determine whether neoadjuvant therapy with 4 cycles of at least one dose of sotorasib plus cisplatin (or carboplatin) and pemetrexed can be administered safely and result in improved MPR rate in patients with KRAS p.G12C-mutant non-squamous NSCLC compared with the historical control MPR rate for platinum-based chemotherapy alone.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Patients with surgically resectable KRAS p.G12C-mutant non-squamous NSCLC as assessed by major pathologic response rate in resected tumor specimens

  through study completion, an average of 1 year

Study Arms (1)

Sotorasib in Combination with Cisplatin/Carboplatin and Pemetrexed

EXPERIMENTAL

4 cycles of at least one dose of sotorasib plus cisplatin (or carboplatin) and pemetrexed can be administered safely

Drug: AMG 510; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

Interventions

AMG 510 DRUG

Given by IV

Sotorasib in Combination with Cisplatin/Carboplatin and Pemetrexed

Cisplatin DRUG

Given by IV

Also known as: Platinol®-AQ, Platinol®, CDDP

Sotorasib in Combination with Cisplatin/Carboplatin and Pemetrexed

Carboplatin DRUG

Given by IV

Sotorasib in Combination with Cisplatin/Carboplatin and Pemetrexed

Pemetrexed DRUG

Given by IV

Also known as: LY231514, Alimta®, MTA, Multitargeted Antifolate, NSC-698037

Sotorasib in Combination with Cisplatin/Carboplatin and Pemetrexed

Eligibility Criteria

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

You may qualify if:

• \[\*\] Subject or subject's legally acceptable representative has provided signed and dated written informed consent prior to initiation of any study specific activities/procedures in accordance with ICH-GCP guidelines and the local legislation.
• \[\*\]Age \> 18 years old.
• \[\*\]Histologically or cytologically confirmed previously untreated non-squamous non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study. Pure squamous cell carcinomas are not eligible but mixed histologies (for example adenosquamous carcinoma) are eligible. Sarcomatoid carcinomas are not eligible.
• Neuroendocrine carcinomas are not eligible. Carcinomas with neuroendocrine differentiation are eligible. Patients with mixed small-cell lung cancer and NSCLC are not eligible.
• Identification of a KRAS p.G12C mutation in tumor tissue or plasma by an approved diagnostic device for detection of KRAS p.G12C in NSCLC or through any nucleic acid-based diagnostic testing method \[including droplet-digital PCR, real-time PCR based methods such as the Idylla KRAS Mutation Assay (Biocartis), tissue and circulating tumor DNA -based next generation sequencing, Sanger-sequencing etc\] performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited laboratory. Patients meeting \[\*\] highlighted criteria will be offered study-provided droplet digital PCR or alternative PCR-based method such as the Idylla KRAS Mutation Assay (Biocartis) for detection of KRAS p.G12C using tumor tissue (1st choice if adequate tissue is available) or plasma (if tumor tissue is not available or cannot be accessed within 5 working days). Turnaround time for reporting of the presence or absence of a KRAS p.G12C mutation will be ≤ 5 working daysfor plasma-based testing and ≤7 working days from the date of confirmation of tissue availability for tissue-based testing. If analysis of tumor tissue fails due to technical reasons, the same patient can undergo analysis of circulating tumor DNA using droplet-digital PCR or alternative PCR-based method such as the Idylla KRAS Mutation Assay (Biocartis). If plasma-based analysis failes to detect a KRAS p.G12C mutation and tumor tissue becomes available, the same patient can undergo analysis of tumor tissue using droplet digital PCR or alternative PCR-based method such as the Idylla KRAS Mutation Assay (Biocartis).
• Patients with disease stage IIA to select stage IIIB (T3-4N2) (according to version 8 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology \[IASLC Staging Manual in Thoracic Oncology 2016\]). Patients with multistation N2 disease are eligible provided that complete surgical resection is considered feasible by multidisciplinary evaluation which must include a thoracic surgeon that performs lung cancer surgery as a prominent part of his/her practice Invasive mediastinal staging with endosonography (EBUS or EUS) with fine-needle aspiration (FNA) and/or mediastinoscopy should be completed within 42 days from the start of treatment in the following cases:
• In case of mediastinal lymph nodes that are enlarged by CT criteria and/or PET-positive mediastinal lymph nodes.
• In case of tumors \> 3 cm in maximum diameter
• In case of centrally located tumors
• For tumors with N1 nodes (cN1) Invasive mediastinal staging should include evaluation of contralateral stations 2 and/or 4 to exclude N3 disease as well as of subcarinal (station 7) lymph nodes. When there are no enlarged mediastinal lymph nodes by CT criteria and there is no uptake on PET/CT (cN0) direct surgical resection with lymph node dissection is indicated for tumors ≤ 3cm that are located in the outer third of the lung.
• \[\*\] Absence of unequivocal evidence of stage IV disease based on contrast-enhanced CT chest, abdomen, pelvis or PET/CT and brain MRI with IV contrast (or contrast-enhanced CT of the head) performed within 60 days is sufficient for study registration but must be confirmed with whole-body PET/CT as well as contrast-enhanced CT chest and abdomen (or contrast-enhanced CT chest including the whole liver and both adrenal glands) and brain MRI with IV contrast (or contrast-enhanced CT of the head) within 28 days prior to the start of treatment. Patients with lesions that are considered equivocal for metastatic disease in the opinion of the local principal investigator are elibile to register and undergo molecular testing if they meet all other \[\*\] marked criteria but must meet the full trial eligibility criteria prior to study enrollment. In patients with severe allergy to iodinated contrast absence of stage IV disease on PET/CT and brain MRI with IV contrast performed within 28 days prior to enrollment suffices to satisfy this eligibility criterion.
• \[\*\]Measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
• \[\*\]The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
• \[\*\]ECOG performance status score 0-1and life expectancy \> 3 months (in the opinion of the investigator).
• \[\*\]Patients must be able to take oral medications and willing to record daily adherence to investigational product.

You may not qualify if:

• \[\*\]Current or prior systemic anticancer therapy (chemotherapy, immunotherapy, biological therapy, hormonal therapyor other investigational anti-cancer drug) or radiation therapy for treatment of the current lung cancer. Concurrent use of hormonal therapy for non-cancer-related conditions (such as hormone replacement therapy) is allowed.
• \[\*\]Pure squamous or predominantly squamous cardinoma histology NSCLC. Mixed tumors with be categorized by the predominant cell type. Subjects with mixed small cell lung cancer and NSCLC histology or large cell neuroendocrine carcinoma histology are ineligible. Subjects with sarcomatoid carcinoma are ineligible.
• The subject is deemed to have unresectable NSCLC by multidisciplinary evaluation that must include a thoracic surgeon who performs lung cancer surgery as a significant part of their practice.
• Stage IIIB N3 and Stages IIIC, IVA and IVB NSCLC.
• \[\*\]History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years.
• \[\*\]History of other malignancy with the following exceptions:
• Treated malignancy with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer (basal or squamous cell cancer) or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Adequately treated breast ductal carcinoma in situ without evidence of disease.
• Prostatic intraepithelial neoplasia without evidence of prostate cancer.
• Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ.
• Major surgery within 28 days of cycle 1 day 1. In addition, patients with ongoing clinically relevant complications from prior surgery are not eligible and they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• \[\*\]Gastrointestinal (GI ) tract disease causing inability to take oral medication, refractory nausea and vomiting, uncontrolled diarrhea, significant small bowel resection or gastric bypass surgery, use of feeding tubes, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease (for example Crohn's disease, ulcerative colitis).
• Infections requiring more than 5 days of parenteral antibiotics, antivirals, or antifungals within 2 weeks prior to cycle 1 day 1. Anti-infective therapy must be completed at least 7 days before cycle 1 day 1. Prophylactic antibiotics are allowed following approval by the trial PI.

Sponsors & Collaborators

• Amgen: collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (2)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

sotorasib; Cisplatin; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Ferdinandos Skoulidis, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ferdinandos Skoulidis, MD,PHD

CONTACT

(713) 792-6363; fskoulidis@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: November 12, 2021
• Study Start: March 30, 2022
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): October 20, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (2)