A Phase II Study of Neoadjuvant Sotorasib in Combination With Cisplatin or Carboplatin and Pemetr… (NCT05118854) | Clinical Trial Compass
RecruitingPhase 2
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
United States27 participantsStarted 2022-03-30
Plain-language 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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. \[\*\] 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.
✓. 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).
What they're measuring
1
Patients with surgically resectable KRAS p.G12C-mutant non-squamous NSCLC as assessed by major pathologic response rate in resected tumor specimens
Timeframe: through study completion, an average of 1 year
✓. 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:
✓. \[\*\] 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.
Exclusion criteria
✕. \[\*\]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:
✕. 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.
✕. \[\*\]Significant cardiovascular disease, such as New York Heart Association cardiac disease (\> Class II), myocardial infarction within 6 months prior to cycle 1 day 1, unstable angina or unstable/uncontrolled cardiac arrhythmias. Patients with cardiac arrhythmias that are adequately controlled with medication (for example chronic, rate controlled atrial fibrillation) are potentially eligible if they are deemed to be surgical candidates and do not meet other exclusion criteria. Patients with 1st degree atrioventricular \[AV\] block or asymptomatic left anterior fascicular block \[LAFB/right bundle branch block \[RBBB\] are eligible.