A Study Comparing Sotorasib With Durvalumab in People With Non-Small Cell Lung Cancer (NSCLC)

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06333678
• Other study ID #: 22-321
• Status: Recruiting
• Phase: Phase 2
• Start date: March 20, 2024
• Est. completion date: March 2027

Study information

• Verified date: March 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Narek Shaverdian, MD
• Phone: 631-212-6323
• Email: shaverdn[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, the researchers will look at whether having participants switch from durvalumab to sotorasib when they have detectable minimal residual disease (MRD) is an effective treatment approach for locally advanced non-small cell lung cancer (LA-NSCLC). The researchers will see whether this switch to sotorasib can control LANSCLC longer compared to the treatment approach of staying on durvalumab (and not switching to sotorasib).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 2027
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Durvalumab
10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.
• Sotorasib
960 mg, Patients who do not tolerate sotorasib at 960 mg can be dose reduced to 120 mg.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (All Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (All Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (All Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	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	Incidence of dose-limiting toxicity (DLT)	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

External Links

•   Memorial Sloan Kettering Cancer Center