This is a multicenter, two part (Part A and Part B) clinical study of CMP-001 administered intratumorally (IT) and subcutaneously (SC) in combination with atezolizumab with or without radiation therapy in participants with NSCLC.
Former Sponsor Checkmate Pharmaceuticals This study will be conducted in two parts, run sequentially: Part A of the study will evaluate the safety and preliminary signs of efficacy for the combination of CMP-001 and atezolizumab. Part B of the study will evaluate the addition of radiation therapy to the combination of CMP-001 and atezolizumab. Each part of the study will follow a Simon 2-stage Optimal Design approach. Part A and Part B of the study will commence with a safety run in of 5 participants treated with the combination treatment (CMP-001 and atezolizumab in Part A; and CMP-001, atezolizumab and radiation therapy in Part B). After the first 5 participants have passed a safety dose-limiting toxicity (DLT) observation period of 30 days and upon approval from the Safety Review Committee (SRC), both parts of the study will continue with enrollment of an additional 7 participants in each part to complete Stage 1 of respective parts. If an acceptable safety profile is established and at least 2 responders out of 12 evaluable participants (that is, complete and partial responders based on Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1 \[v1.1\] or RECIST v1.1 for immune-based therapeutics \[iRECIST\] criteria) in Stage 1), the study will enroll an additional 23 evaluable participants in Stage 2 of each part. A maximum of 35 evaluable participants will be enrolled in each Part A and Part B. Participants enrolled in Part A with documented progression per RECIST v1.1 on the combination of CMP-001 and atezolizumab have the option to receive radiation therapy add-on treatment after documented disease progression per computed tomography (CT)/magnetic resonance imaging (MRI) or positron emission tomography (PET) scan. The total number of participants enrolled into the Part A optional radiation therapy add-on may not exceed the total number of participants enrolled in Part A. Enrollment of participants in Part A optional radiation therapy add-on will not affect enrollment in Part B of the study as these participants will be evaluated separately. Participants will continue treatment with CMP-001 in combination with atezolizumab as long as they do not experience unacceptable toxicities and when, according to the Investigator, continued treatment is in the participant's best interest.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
CMP-001 will be administered as per the dose and schedule specified in the respective arms.
Atezolizumab will be administered as per the approved label and according to the schedule specified in the respective arms.
Radiation therapy will be administered using either 3-dimensional (3D) conformal radiotherapy or intensity-modulated radiation therapy (IMRT) to non-target node or metastatic lesion as per the dose and schedule specified in the respective arms.
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
City of Hope Medical Center
Duarte, California, United States
University of Colorado Aurora
Aurora, Colorado, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Part A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs will be evaluated and assigned a grade using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (up to approximately 2 years 9 months)
Part A and B: DLT
Time frame: First 30 days of therapy starting from Week 1 Day 1
Part A and B: Oral Temperature
Oral temperature should be measured in supine or seated position, following at least 3 minutes of rest.
Time frame: From screening up to end of treatment (EOT) (up to approximately 2 years 9 months)
Part A and B: Respiratory Rate
Respiratory rate should be measured in supine or seated position, following at least 3 minutes of rest.
Time frame: From screening up to EOT (up to approximately 2 years 9 months)
Part A and B: Systolic and Diastolic Blood Pressure
Blood pressure should be measured in supine or seated position, following at least 3 minutes of rest.
Time frame: From screening up to EOT (up to approximately 2 years 9 months)
Part A and B: Body Weight
Physical examination included body weight measurement.
Time frame: From screening up to EOT (up to approximately 2 years 9 months)
Part A and B: Body Mass Index (BMI)
Physical examination included BMI measurement.
Time frame: From screening up to EOT (up to approximately 2 years 9 months)
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MD Anderson
Houston, Texas, United States
Part A and B: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Parameters
ECG parameters will include heart rate and PR, QRS, QT, and QT corrected for heart rate (QTc) intervals. QT will be corrected using Fridericia's (QTcF) formula. ECG will be performed after the participant has been resting in supine or semi-supine position for at least 5 minutes.
Time frame: From screening up to EOT (up to approximately 2 years 9 months)
Part A and B: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters
Clinical laboratory parameters include serum chemistry, hematology, and urinalysis.
Time frame: From screening up to EOT (up to approximately 2 years 9 months)
Part A and B: Concentration of Chemokine IP-10
Time frame: Day 1 of Weeks 1, 3, 8, and Day 2 of Weeks 3, 8
Part A and B: Objective Response Rate (ORR) (Percentage of Participants With Objective Response) as per RECIST V1.1 or iRECIST Using CT/PET or MRI Scans
ORR will be calculated as the number of participants with a confirmed complete response (CR) or partial response (PR) divided by the number of participants dosed.
Time frame: Baseline until confirmed disease progression (CR or PR) or death, whichever occur first (assessment at every 9 weeks throughout the study from Week 1 Day 1, up to approximately 2 years 9 months
Part A and B: Time to Response (TTR) as per RECIST V1.1 or iRECIST Using CT/PET or MRI Scans
Time frame: From first dose of CMP-001 until disease progression or death, whichever occur first (assessment at every 9 weeks throughout the study from Week 1 Day 1, up to approximately 2 years 9 months)
Part A and B: Duration of Response (DOR) as per RECIST V1.1 or iRECIST Using CT/PET or MRI Scans
Time frame: From the date of first confirmed CR or PR until the first date of recurrent or progressive disease (assessment at every 9 weeks throughout the study from Week 1 Day 1, up to approximately 2 years 9 months)