- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06333678
A Study Comparing Sotorasib With Durvalumab in People With Non-Small Cell Lung Cancer (NSCLC)
A Randomized Phase II Study of Sotorasib Versus Continued Consolidation Durvalumab in Patients With KRAS G12C Mutant Locally Advanced Non-small Cell Lung Cancer (LANSCLC) With Persistent ctDNA Defined Minimal Residual Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
In the first phase of the randomized trial, defined as the Pre-Monitoring Phase, patients with LANSCLC with a KRAS G12C mutation who are planned to undergo, are undergoing, or very recently completed definitive chemoradiation with the plan for durvalumab consolidation are enrolled. Chemoradiation treatment and all clinical assessments during the Pre-Monitoring Phase are per standard of care as per institutional standards.
Patients who (1) complete chemoradiation, (2) have detectable ctDNA post chemoradiation, (3) are without evidence of progressive disease on imaging, (4) and are planned to start durvalumab consolidation then continue into the Monitoring Phase. All other patients are no longer on trial and are taken off study. Patients in the Monitoring Phase will have ctDNA measured again early-on during durvalumab consolidation (i.e. cycle 3 of durvlalumab +/- 2 weeks) in conjunction with standard of care imaging. Patients with MRD will then continue to the Randomization Phase of trial.
In the Randomization Phase patients will be randomized in a 1:1 fashion to continue standard of care durvalumab (group 1) vs. switch to sotorasib at 960 mg daily (group 2), with the primary endpoint of PFS. Patients switching to sotorasib will undergo a 28-day durvalumab washout and will receive sotorasib at 960 mg daily until progression. Washout will be confirmed by ensuring that cycle 1, day 1 of sotorasib is scheduled for at least 28 days after the most recent durvalumab dose.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Bob Li, MD
- Phone Number: 646-608-3791
Study Contact Backup
- Name: Narek Shaverdian, MD
- Phone Number: 631-212-6323
- Email: shaverdn@mskcc.org
Study Locations
-
-
New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Recruiting
- Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
-
Contact:
- Narek Shaverdian, MD
- Phone Number: 631-212-6323
-
Middletown, New Jersey, United States, 07748
- Recruiting
- Memorial Sloan Kettering Monmouth (All Protocol Activities)
-
Contact:
- Narek Shaverdian, MD
- Phone Number: 631-212-6323
-
Montvale, New Jersey, United States, 07645
- Recruiting
- Memorial Sloan Kettering Bergen (All Protocol Activities)
-
Contact:
- Narek Shaverdian, MD
- Phone Number: 631-212-6323
-
-
New York
-
Commack, New York, United States, 11725
- Recruiting
- Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
-
Contact:
- Narek Shaverdian, MD
- Phone Number: 631-212-6323
-
Harrison, New York, United States, 10604
- Recruiting
- Memorial Sloan Kettering Westchester (All Protocol Activities)
-
Contact:
- Narek Shaverdian, MD
- Phone Number: 631-212-6323
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center (All Protocol Activities)
-
Contact:
- Narek Shaverdian, MD
- Phone Number: 631-212-6323
-
Uniondale, New York, United States, 11553
- Recruiting
- Memorial Sloan Kettering Nassau (All Protocol Activities)
-
Contact:
- Narek Shaverdian, MD
- Phone Number: 631-212-6323
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Pre-Monitoring Phase
- Histologic diagnosis of NSCLC
- Locally advanced disease, defined as AJCC 8th Edition Stage III disease.
Plan for, currently receiving, or recently completed definitive chemoradiation. Definitive radiation is defined as 56-70 Gy in 28-35 fractions concurrently with one of the following chemotherapy regimens:
- Carboplatin + pemetrexed
- Cisplatin + pemetrexed
- Paclitaxel + carboplatin
- Cisplatin + etoposide
- KRAS p.G12C mutation identified through molecular testing
- Adequate hepatic function, with adequate function defined as AST and ALT < 2.5 x the upper limit of normal (ULN)
- Patient eligible for consolidative durvalumab therapy
- ECOG Performance status 0 - 2.
- Age ≥ 18 years.
- Patients must have decision-making capacity to consent to the study.
- Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: >/= 55 years old and no menses for 1> year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral salpingectomy OR history of bilateral oophorectomy) or must be willing to comply with contraception requirements.
Monitoring Phase
Completed definitive chemoradiation. Definitive radiation is defined as 56-70 Gy in 28-35 fractions concurrently with one of the following chemotherapy regimens:
- Carboplatin + pemetrexed
- Cisplatin + pemetrexed
- Paclitaxel + carboplatin
- Cisplatin + etoposide
- Detectable ctDNA measured within 8 weeks (+2 weeks) of completing definitive chemoradiation
- No evidence of radiographic progression, as measured through SOC imaging, as deemed by principal investigator, including a CT scan of the chest
- ECOG Performance status 0 - 2.
- Plan to start durvalumab consolidation
Therapeutic Phase
- No evidence of radiographic RECIST 1.1 progression, as measured through SOC imaging, as deemed by principal investigator, including a CT scan of the chest
- MRD as measured by ctDNA testing (described above)
- Candidate for sotorasib therapy
- Must have a negative pregnancy test (serum or urine) within 3 days prior to the first dose of sotorasib (if assigned to Group 2).
Exclusion Criteria:
- Serious medical co-morbidities precluding radiotherapy, determined at the discretion of the treating investigator.
- Pregnant or lactating women.
- Physical limitation to undergo radiotherapy.
- Other active malignancy (e.g. receiving active treatment) within the last year except for basal cell carcinoma of the skin and in situ malignancy even if without evidence of disease and patients on adjuvant hormonal therapies (e.g. breast, prostate), or bladder cancer with localized diseases
- Prior pneumonitis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: continue standard of care (SOC) durvalumab treatment
Will continue to receive durvalumab, 10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.
|
10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.
|
Experimental: switch sotorasib treatment until progression
Will receive sotorasib at 960 mg daily until progression.
A dose de-escalation regimen based on toxicity will be implemented as below.
If 120 mg cannot be tolerated, sotorasib will be discontinued and the patient will be removed from the trial.
|
960 mg, Patients who do not tolerate sotorasib at 960 mg can be dose reduced to 120 mg.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: up to 3 years
|
PFS will be defined as the time from randomization until progression or death , or from the time of randomization until the last follow up imaging (if no progression and alive).
Progression will be evaluated by RECIST 1.1 guidelines.
|
up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of dose-limiting toxicity (DLT)
Time Frame: 1 month after starting Sotorasib
|
which we define as a hospitalization, life threatening condition, any death not clearly due to the underlying disease or extraneous causes, or therapy-related grade 3 or higher non-hematologic toxicity.
The study will continue if the definition of "acceptable safety" is met.
|
1 month after starting Sotorasib
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Narek Shaverdian, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Durvalumab
- Sotorasib
Other Study ID Numbers
- 22-321
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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