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

NCT03438318 | Completed Phase 1 FDA Drug

• 1 other identifier: CMP-001-003
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  First 30 days of therapy starting from Week 1 Day 1

Secondary Outcomes (11)

• Part A and B: Oral Temperature

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

• Part A and B: Respiratory Rate

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

• Part A and B: Systolic and Diastolic Blood Pressure

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

• Part A and B: Body Weight

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

• Part A and B: Body Mass Index (BMI)

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

Study Arms (2)

Part A (CMP-001, Atezolizumab and Optional Radiation Therapy)

EXPERIMENTAL

Participants 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.

Drug: CMP-001; Drug: Atezolizumab; Radiation: Radiation Therapy

Part B (Radiation Therapy, CMP-001 and Atezolizumab)

EXPERIMENTAL

Participants 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.

Drug: CMP-001; Drug: Atezolizumab; Radiation: Radiation Therapy

Interventions

CMP-001 DRUG

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

Part A (CMP-001, Atezolizumab and Optional Radiation Therapy); Part B (Radiation Therapy, CMP-001 and Atezolizumab)

Atezolizumab DRUG

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

Part A (CMP-001, Atezolizumab and Optional Radiation Therapy); Part B (Radiation Therapy, CMP-001 and Atezolizumab)

Radiation Therapy RADIATION

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.

Part A (CMP-001, Atezolizumab and Optional Radiation Therapy); Part B (Radiation Therapy, CMP-001 and Atezolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically confirmed diagnosis of metastatic NSCLC.
• 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.
• 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).

You may not qualify if:

• 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:
• days from prior tyrosine kinase inhibitor (TKI) depending on half-life.
• weeks from prior chemotherapy.
• 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.
• 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).

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Novella Clinical: collaborator

Study Sites (5)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Colorado Aurora

Aurora, Colorado, 80045, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 36925644 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2018
• First Posted: February 19, 2018
• Study Start: March 15, 2018
• Primary Completion: December 11, 2019
• Study Completion: December 11, 2019
• Last Updated: August 3, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

US (5)