Clinical trial NCT06333678: A Study Comparing Sotorasib With Durvalumab in People With Non-Small Cell Lung Cancer (NSCLC)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Sotorasib
Durvalumab
Locally advanced disease
KRAS p.G12C mutation
22-321
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2024-03-27
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase II randomized trial
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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 or already started 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: up to 3 years
Secondary outcomes:
measure: Incidence of dose-limiting toxicity (DLT)
timeFrame: 1 month after starting Sotorasib
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami (Data Collection Only)
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan (Data Collection Only)
state: Michigan
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (All Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (All Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (All Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (All Protocol Activities)
state: New York
city: Allentown
country: United States
facility: Lehigh Valley Health Network (Data Collection Only)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University (Data Collection Only)
state: Tennessee
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Narek Shaverdian, MD
role: PRINCIPAL_INVESTIGATOR
References: