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Non Small Cell Lung CancerPhase 1NCT03438318

Study Evaluating CMP-001 in Combination With Atezolizumab in Participants With Non-Small Cell Lung Cancer

A Phase 1 study testing CMP-001, Atezolizumab and Radiation Therapy in people with Non Small Cell Lung Cancer, run by Regeneron Pharmaceuticals at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
CMP-001, Atezolizumab and Radiation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
5 sitesUnited States
Study dates
15 Mar 2018to 11 Dec 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histopathologically confirmed diagnosis of metastatic NSCLC.
  • Documented disease progression on prior programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) therapy in any line. Participants must have received a minimum of 4 doses of anti-PD-1/PD-L1 therapy before enrolling into the CMP-001-003 study. If participants have received fewer than 4 doses of anti-PD-1/PD-L1 therapy, documented radiologic progression and sponsor approval is necessary prior to inclusion.
  • Participants with epidermal growth factor (EGFR) activating mutations, EGFR T790M or anaplastic lymphoma kinase (ALK) gene re-arrangement must have received prior standard of care and have evidence of disease progression. With the exception of participants with squamous cell cancer, EGFR and ALK status must be known prior to enrollment.
  • Participants must have at least one extra-central nervous system (CNS), non-bone tumor lesion amenable for IT injection greater than or equal to (>=) 1.5 centimeters (cm) and that is not in close proximity or encasing crucial structures such as major blood vessels, trachea, nerve bundles.
  • Measurable disease per RECIST version 1.1.
  • Capable of understanding and complying with protocol requirements.
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  • A life expectancy of greater than 24 weeks at Screening.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at Screening.
  • Most recent laboratory values within 2 weeks prior to Week 1 Day 1 meet the following standards:
  • Bone marrow function: Neutrophil count >=1,500/ cubic millimeters (mm^3) without granulocyte colony stimulating factor; Platelet count >=100,000/mm^3 without transfusion; Hemoglobin concentration >=9.0 grams per deciliter (g/dL).
  • Liver function: Total bilirubin less than or equal to (<=) 2.0 times the upper limit of normal (ULN) of each institution with the exception of participants with Gilbert Disease serum bilirubin >= 3 * ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5 times the ULN with the following exceptions: participants with documented liver metastases; AST and ALT <=5 * ULN.
  • Renal function: serum creatinine <=1.5 times the ULN.
  • Lactate dehydrogenase (LDH) <=2 times ULN.
  • Partial thromboplastin time (PTT) and international normalized ratio (INR): Activated PTT (aPTT) <=1.5 * ULN, unless related to lupus anticoagulant. Participants receiving unfractionated heparin must have aPTT between 1.5 and 2.5 * ULN or determined by their physician; INR < =1.5 * ULN. Participants receiving warfarin should have INR between 2.0 and 3.0 or within a range determined by their physician.
  • The participant must sign a written informed consent form prior to the initiation of any study procedures. Adult participants unable to provide written informed consent on their own behalf will not be eligible for the study.
  • For participants enrolled in Part B, metastatic lesions must be accessible for radiation therapy (that is, no direct overlap of the current treatment).

Who cannot join

  • Pregnant or breastfeeding
  • Received investigational therapy (that is, small molecule or biologic) within 30 days prior to the start of CMP-001 dosing on Week 1 Day 1. However, if an investigational therapy has a short half-life, a reduced wash out period may be acceptable with Sponsor approval. Acceptable washout periods for non-investigational therapy include:
  • 3-14 days from prior tyrosine kinase inhibitor (TKI) depending on half-life.
  • 3 weeks from prior chemotherapy.
  • 1 week for prior palliative radiation therapy, or 2 weeks if prior brain radiation therapy.
  • Received treatment with anti- cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody within 30 days prior to the start of CMP-001.
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  • 14 days for prior PD-1 therapy.
  • Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). If there is no known or documented history of HIV, HBV or HCV, the site is not required to do additional testing for these values at Screening.
  • Developed autoimmune disorders of Grade 4 while on prior immunotherapy. Participants who developed autoimmune disorders, of Grade <=3 may enroll if the disorder has resolved to Grade <=1 and the participant has been off systemic steroids at doses greater than (>) 10 milligrams per day (mg/day), for the treatment of the autoimmune disorder, for at least 2 weeks.
  • Require systemic pharmacologic doses of corticosteroids greater than the equivalent of 10 mg/day prednisone; topical, ophthalmologic and inhalational steroids are permitted. Participants who have a history of adrenal insufficiency and are receiving greater than 10 mg/day prednisone may be eligible but only after Sponsor consultations. Participants who are currently receiving steroids at a dose of <=10 mg/day do not need to discontinue steroids prior to enrollment.
  • Active (that is, symptomatic or progressing) CNS metastases. However, participants with active CNS metastases are eligible for the trial if:
  • The metastases have been treated by surgery and/or radiotherapy.
  • The participant is off corticosteroids of >10 mg/day prednisone or equivalent.
  • The participant is neurologically stable for at least 2 weeks prior to Screening.
  • Brain MRI completed within 6 weeks of Screening (required for all participants).
  • Any concurrent uncontrolled illness, including mental illness or substance abuse, which in the opinion of the Investigator, would make the participant unable to cooperate or participate in the trial.
  • Severe uncontrolled cardiac disease within 6 months of screening, including but not limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or cerebrovascular accident (CVA).
  • Requires prohibited treatment (that is., non-protocol specified anticancer pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant tumor). Limited field single dose radiotherapy for pain palliation would be allowed at any time during the course of treatment.
  • Women of childbearing potential who are unable or unwilling to use an acceptable method of contraception.
  • Requires continuous anti-coagulation or anti-platelet therapy that cannot be safely interrupted to allow for IT injection and/or history of coagulopathy.
  • History of another malignancy except for:
  • Malignancy treated with curative intent and with no known active disease >5 years prior to the start of CMP-001 dosing on Week 1 Day 1 and of low potential risk for recurrence.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease (for example, cervical cancer in situ), superficial bladder cancer, squamous cell carcinoma of the skin, basal cell carcinoma of the skin.
  • Other concurrent low-grade malignancies such as chronic lymphocytic leukemia (CLL) (Rai 0) may be considered after discussion and permission from Sponsor.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Colorado Aurora

    Aurora, Colorado, 80045

  • City of Hope Medical Center

    Duarte, California, 91010

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • MD Anderson

    Houston, Texas, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

Other trials in United States

About this study

Official title: A Multicenter, Two-Part, Phase 1B Clinical Study of CMP-001 in Combination With Atezolizumab With and Without Radiation Therapy in Subjects With Advanced Non Small Cell Lung Cancer (NSCLC)

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.

Read the detailed description

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.

Being tested
CMP-001, Atezolizumab, Radiation Therapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CMP-001Drug

    CMP-001 will be administered as per the dose and schedule specified in the respective arms.

  • AtezolizumabDrug

    Atezolizumab will be administered as per the approved label and according to the schedule specified in the respective arms.

  • Radiation TherapyRadiation

    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.

Study groups in NCT03438318
Study groupRoleWhat they receive
Part A (CMP-001, Atezolizumab and Optional Radiation Therapy)ExperimentalParticipants will receive CMP-001 5 milligrams (mg) SC once weekly for 2 weeks, then 10 mg IT once weekly for 3 weeks, followed by every 3 weeks thereafter until discontinuation of treatment in combination with atezolizumab SC every 3 weeks starting at Week 2. Route of administration (IT/SC) for CMP-001 beyond Week 5 will be determined by Investigator. Participants enrolled in Part A who progressed per RECIST v1.1 on combination of CMP-001 and atezolizumab have opportunity to enroll in Part A optional radiation therapy add-on after documented disease progression per CT/MRI or PET scan. After CMP-001 washout period of 10 days, participants will be treated with radiation consisting of 20 grays in 5 fractions for 5 days then resume CMP-001 treatment.
Receives: Drug: CMP-001; Drug: Atezolizumab; Radiation: Radiation Therapy
Part B (Radiation Therapy, CMP-001 and Atezolizumab)ExperimentalParticipants will be treated with radiation therapy consisting of 20 grays in 5 fractions for 5 days, then participants will receive CMP-001 5 mg SC once weekly for 2 weeks, then 10 mg IT once weekly for 3 weeks, followed by dosing every 3 weeks thereafter until discontinuation of treatment. The route of administration (that is, IT or SC) for CMP-001 beyond Week 5 will be determined by the Investigator. First dose of CMP-001 will be administered within 2 days of radiation therapy. Atezolizumab will be administered SC in combination with CMP-001 every 3 weeks starting at Week 2.
Receives: Drug: CMP-001; Drug: Atezolizumab; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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)

  2. Part A and B: DLT

    Measured: First 30 days of therapy starting from Week 1 Day 1

Secondary outcomes (11)

  1. Part A and B: Oral Temperature

    Oral temperature should be measured in supine or seated position, following at least 3 minutes of rest.

    Measured: From screening up to end of treatment (EOT) (up to approximately 2 years 9 months)

  2. Part A and B: Respiratory Rate

    Respiratory rate should be measured in supine or seated position, following at least 3 minutes of rest.

    Measured: From screening up to EOT (up to approximately 2 years 9 months)

  3. 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.

    Measured: From screening up to EOT (up to approximately 2 years 9 months)

  4. Part A and B: Body Weight

    Physical examination included body weight measurement.

    Measured: From screening up to EOT (up to approximately 2 years 9 months)

  5. Part A and B: Body Mass Index (BMI)

    Physical examination included BMI measurement.

    Measured: From screening up to EOT (up to approximately 2 years 9 months)

  6. 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.

    Measured: From screening up to EOT (up to approximately 2 years 9 months)

  7. Part A and B: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters

    Clinical laboratory parameters include serum chemistry, hematology, and urinalysis.

    Measured: From screening up to EOT (up to approximately 2 years 9 months)

  8. Part A and B: Concentration of Chemokine IP-10

    Measured: Day 1 of Weeks 1, 3, 8, and Day 2 of Weeks 3, 8

  9. 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.

    Measured: 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

  10. Part A and B: Time to Response (TTR) as per RECIST V1.1 or iRECIST Using CT/PET or MRI Scans

    Measured: 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)

  11. Part A and B: Duration of Response (DOR) as per RECIST V1.1 or iRECIST Using CT/PET or MRI Scans

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2018
  2. Study start15 Mar 2018
  3. Primary completion11 Dec 2019
  4. Study completion11 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03438318
Sponsor's protocol ID
CMP-001-003
Status last verified
Aug 2022
First submitted
25 Jan 2018
Last updated
3 Aug 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Negrao MV, Papadimitrakopoulou VA, Price AC, Tam AL, Furqan M, Laroia ST, Massarelli E, Pacheco J, Heymach JV, Tsao AS, Walker GV, Vora L, Mauro D, Kelley H, Wooldridge JE, Krieg AM, Niu J. Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With Programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Blockade-Resistant Advanced NSCLC. JTO Clin Res Rep. 2022 Oct 26;4(3):100423. doi: 10.1016/j.jtocrr.2022.100423. eCollection 2023 Mar.

    PubMed 36925644

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CMP-001, Atezolizumab and Radiation Therapy in people with Non Small Cell Lung Cancer, run by Regeneron Pharmaceuticals at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03438318, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2022.

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