M7824 in Patients With Metastatic Colorectal Cancer or With Advanced Solid Tumors With Microsatellite Instability

NCT03436563 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2017-0339NCI-2018-00919
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies how well anti-PD-L1/TGFbetaRII fusion protein M7824 (M7824) works in treating patients with colorectal cancer (or with other solid tumors with microsatellite instability) that has spread to other places in the body or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as M7824, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Colon Adenocarcinoma; High-Frequency Microsatellite Instability; Metastatic Malignant Solid Neoplasm; Rectal Adenocarcinoma; Refractory Colorectal Carcinoma; Stage IV Colon Cancer AJCC v8; Stage IV Rectal Cancer AJCC v8; Stage IVA Colon Cancer AJCC v8; Stage IVA Rectal Cancer AJCC v8; Stage IVB Colon Cancer AJCC v8; Stage IVB Rectal Cancer AJCC v8

Keywords

colon cancer; rectal cancer; colorectal cancer; microsatellite instability; circulating tumor DNA; metastasis; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Circulating DNA Clearance

  Defined as the percentage of somatic mutations, ctDNA that is eliminated in blood as well as no appearance of any new somatic mutations following six doses of BA in the study participants.

  Baseline up to 12 weeks

Secondary Outcomes (3)

• Overall Survival (OS)

  Baseline up to 2 years

• Grade 3 or Higher A/E Per CTCAE v4.03

  Start of study treatment up to 28 days after end of treatment

• Disease-Free Survival (DFS)

  Baseline up to 2 years

Study Arms (1)

Treatment (M7824)

EXPERIMENTAL

Patients receive M7824 IV over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity (Cohorts A,B, and C) or for six doses in patients with detectable circulating tumor DNA (ctDNA) following resection of all known liver metastases (Cohort D).

Biological: Anti-PD-L1/TGFbetaRII Fusion Protein M7824

Interventions

Anti-PD-L1/TGFbetaRII Fusion Protein M7824 BIOLOGICAL

Given IV

Also known as: Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C, Bintrafusp Alfa

Treatment (M7824)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum that is metastatic or unresectable (cohorts A,B); histologically or cytologically confirmed carcinoma not originating in the colon or rectum (cohort C); or histologically or cytologically confirmed adenocarcinoma of the colon or the rectum following resection of the primary tumor and metastatic disease, following completion of standard-of-care perioperative therapy at the discretion of the treating provider (cohort D).
• Confirmation of: a) Cohort A: microsatellite instability in colorectal cancer (CRC); b) Cohort B: CMS4 CRC classification on pretreatment primary tumor; c) Cohort C: microsatellite instability in non-CRC solid tumor; d. Cohort D: microsatellite stability.
• Ability to provide written informed consent.
• Documented progression to prior therapies (Cohorts A, B, and C): a) Cohort A: Disease progression following prior immune checkpoint blockade therapy; b) Cohort B: Progression or intolerance to at least 2 prior lines of standard therapy for unresectable or metastatic CRC; c) Cohort C: Disease progression following prior immune checkpoint blockade therapy.
• Available primary tumor tissue for CMS4 biomarker assessment.
• Life expectancy \>= 12 weeks as judged by the treating physician.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1(Cohorts A, B, and C). For cohort B, measureable lesions must be identified apart from the irradiated tumor lesion. Patients in cohort D must have no evidence of radiographically evident disease at the time of study entry.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (in absence of blood transfusion).
• Lymphocyte count \>= 0.5 x 10\^9/L (in absence of blood transfusion).
• Platelet count \>= 100 x 10\^9/L (in absence of blood transfusion).
• Hemoglobin (Hgb) \>= 9 g/dL (in absence of blood transfusion).
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN).
• An aspartate aminotransferase (AST) level =\< 2.5 x ULN, and an alanine aminotransferase (ALT) level =\< 2.5 x ULN. If liver metastases are present, then it is acceptable for AST level =\< 5.0 x ULN, and an ALT level =\< 5.0 x ULN.
• International normalized ratio (INR) \< 1.5.

You may not qualify if:

• Concurrent treatment with non-permitted drugs and other interventions.
• Anticancer treatment within 14 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy \[with the exception of palliative radiotherapy delivered in a normal organ-sparing technique\], immune therapy, or cytokine therapy).
• Major surgery as determined by the investigator within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted).
• Systemic therapy with immunosuppressive agents within 7 days before the start of treatment; or use of any investigational drug within 28 days before the start of trial treatment.
• Cohort A and C only: Intolerance or serious adverse immune related adverse events (irAEs) that were symptomatic or required or continues to require ongoing immunosuppression to previous immune checkpoint therapy.
• Cohort B and D: prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.
• Previous malignant disease (other than the target malignancy to be investigated in this trial) within 3 years prior to study treatment initiation. Subjects with a history of cervical carcinoma in situ, superficial or non-invasive bladder cancer, or basal cell or squamous cell carcinoma in situ, previously treated with curative intent are NOT excluded. Subjects with other localized malignancies treated with curative intent need to be discussed with the principal investigator.
• Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
• Significant acute or chronic infections including, among others: a) Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome; b) Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV DNA or HBV core antibody positive alone with reflex to positive HBV DNA or positive HCV antibody with reflex to positive HCV ribonucleic acid \[RNA\]); c) Subjects with active tuberculosis (history of exposure or history of positive tuberculosis test plus presence of clinical symptoms, physical or radiographic findings).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a) Subjects with type I diabetes, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible; b) Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses =\< 10 mg of prednisone or equivalent per day; c) Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.
• Known severe hypersensitivity reactions to monoclonal antibodies (grade \>= 3 National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] v4.03), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma.
• Persisting toxicity (except alopecia and vitiligo) related to prior oncologic therapy grade \> 1 NCI-CTCAE v4.03, however, sensory neuropathy grade =\< 2 is acceptable.
• Clinically significant cardiovascular/ cerebrovascular disease as follows: cerebral vascular accident / stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification class \> II), or serious cardiac arrhythmia.
• Clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Morris JS, Luthra R, Liu Y, Duose DY, Lee W, Reddy NG, Windham J, Chen H, Tong Z, Zhang B, Wei W, Ganiraju M, Broom BM, Alvarez HA, Mejia A, Veeranki O, Routbort MJ, Morris VK, Overman MJ, Menter D, Katkhuda R, Wistuba II, Davis JS, Kopetz S, Maru DM. Development and Validation of a Gene Signature Classifier for Consensus Molecular Subtyping of Colorectal Carcinoma in a CLIA-Certified Setting. Clin Cancer Res. 2021 Jan 1;27(1):120-130. doi: 10.1158/1078-0432.CCR-20-2403. Epub 2020 Oct 27.

  PMID: 33109741 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Colonic Neoplasms; Neoplasm Metastasis; Rectal Neoplasms; Colorectal Neoplasms; Microsatellite Instability

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Rectal Diseases; Genomic Instability

Results Point of Contact

• Title: Dr. Van Morris
• Organization: M D Anderson Cancer Center

vkmorris@mdanderson.org

713-792-2828

Study Officials

• Van K Morris, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: February 19, 2018
• Study Start: March 7, 2018
• Primary Completion: August 8, 2023
• Study Completion: August 8, 2023
• Last Updated: November 27, 2024
• Results First Posted: November 27, 2024

Record last verified: 2024-11

Locations

US (1)