Trial Title:
A Study Comparing Sotorasib With Durvalumab in People With Non-Small Cell Lung Cancer (NSCLC)
NCT ID:
NCT06333678
Condition:
Non-Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Durvalumab
Sotorasib
Conditions: Keywords:
Sotorasib
Durvalumab
Locally advanced disease
KRAS p.G12C mutation
22-321
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Phase II randomized trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks for up to 12 months.
Arm group label:
continue standard of care (SOC) durvalumab treatment
Intervention type:
Drug
Intervention name:
Sotorasib
Description:
960 mg, Patients who do not tolerate sotorasib at 960 mg can be dose reduced to 120 mg.
Arm group label:
switch sotorasib treatment until progression
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.
Criteria for 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 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Miami (Data Collection Only)
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Dionysios Watson, MD
Email:
dionysios.watson@miami.edu
Facility:
Name:
University of Michigan (Data Collection Only)
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Gregory Kalemkerian, MD
Phone:
734-647-8902
Facility:
Name:
Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Narek Shaverdian, MD
Phone:
631-212-6323
Facility:
Name:
Memorial Sloan Kettering Monmouth (All Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Narek Shaverdian, MD
Phone:
631-212-6323
Facility:
Name:
Memorial Sloan Kettering Bergen (All Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Narek Shaverdian, MD
Phone:
631-212-6323
Facility:
Name:
Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Narek Shaverdian, MD
Phone:
631-212-6323
Facility:
Name:
Memorial Sloan Kettering Westchester (All Protocol Activities)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Narek Shaverdian, MD
Phone:
631-212-6323
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Narek Shaverdian, MD
Phone:
631-212-6323
Facility:
Name:
Memorial Sloan Kettering Nassau (All Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Narek Shaverdian, MD
Phone:
631-212-6323
Facility:
Name:
Vanderbilt University (Data Collection Only)
Address:
City:
Nashville
Zip:
37232
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Ryan Whitaker, MD, PhD
Phone:
615-322-2555
Start date:
March 20, 2024
Completion date:
March 2027
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Amgen
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06333678
http://www.mskcc.org/mskcc/html/44.cfm
