SAR439459 and Cemiplimab for the Treatment of Advanced or Unresectable Solid Tumors, Strategic Alliance, TACTIC TRIAL

NCT04729725 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 2020-0649NCI-2020-10859
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ib trial with SAR439459, a TGF-beta inhibitor, in combination with cemiplimab, a PD-L1 inhibitor, in patients with solid tumors that have spread to other places in the body (advanced) or cannot be removed by surgery (unresectable). Inhibiting TGF-beta may interfere with the ability of cancer cells to grow and spread and may sensitize cancers to immune checkpoint inhibitor therapy. The objective of this study is to determine whether this drug combination is effective in shrinking cancers, keeping them from growing, helping patients live longer, and to see if the drug combination is safe.

Conditions

Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Unresectable Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate (CBR)

  Defined as complete response (CR) + partial response (PR) + stable disease (SD) \> 12 weeks \> 12 weeks assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Will estimate CBR with 95% confidence intervals (CI). Will assess associations between marker levels and outcome using receiver operator characteristics curve analysis, graphical analysis and logistic regression analysis as appropriate.

  12 weeks

Secondary Outcomes (14)

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Up to 1 year after completion of study treatment

• Clinical benefit rate

  Up to 1 year after completion of study treatment

• Overall response rate

  Up to 1 year after completion of study treatment

• Progression free survival

  Up to 1 year after completion of study treatment

• Duration of response

  Up to 1 year after completion of study treatment

Study Arms (1)

Treatment (SAR439459, cemiplimab)

EXPERIMENTAL

Patients receive SAR439459 IV over 30 minutes on day 1 and cemiplimab IV over 30 minutes on day 1 starting cycle 2. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Anti-TGF-beta Monoclonal Antibody SAR-439459; Biological: Cemiplimab

Interventions

Anti-TGF-beta Monoclonal Antibody SAR-439459 BIOLOGICAL

Given IV

Also known as: Anti-TGFb SAR-439459, Anti-transforming Growth Factor-beta mAb SAR439459, SAR 439459, SAR-439459, SAR439459

Treatment (SAR439459, cemiplimab)

Cemiplimab BIOLOGICAL

Given IV

Also known as: Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN2810

Treatment (SAR439459, cemiplimab)

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically confirmed, advanced unresectable or metastatic solid tumor whom in the opinion of the Investigator do not have a suitable alternative therapy
• Disease must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST 1.1), and safely undergo serial tumor biopsies. For patients with castration-resistant prostate cancer, evaluable disease by Prostate Cancer Working Group 3 (PCWG3) will be permitted if serial biopsies (e.g. bone tumor biopsies) are feasible
• Patients must have previously received a PD-1 or PD-L1 inhibitor-based therapy and must have achieved stable disease (SD) for at least 6 months, or complete remission/partial remission (CR/PR) prior to disease progression (secondary resistance) by radiological assessment by the study investigator. The PD-1 or PD-L1 inhibitor-based therapy must be the immediate line of treatment prior to study enrollment
• Patients must have adequate functional status as defined by Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Absolute neutrophil count (ANC) \>= 1,500 /mcL
• Platelets \>= 100,000 / mcL
• Hemoglobin \>= 9.0 g/dL
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (creatinine clearance should be calculated per institutional standard)
• Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \>= 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN
• Patients must have discontinued all previous systemic cancer treatments for at least 21 days and recovered from the acute toxic effects of therapy to grade \< 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, excluding persistent grade 2 or higher toxicities determined to be clinically insignificant per the principal investigator (PI) (i.e. alopecia or grade 2 neuropathy). Patients must have discontinued from previous treatments as shown below:
• Cytotoxic therapies or targeted agents that are small-molecule inhibitors \>= 3 weeks prior to (study entry/enrollment/first dose of study treatment)
• Mitomycin C or nitrosoureas \>= 42 days prior to (study entry/enrollment/first dose of study treatment)

You may not qualify if:

• Patients who are pregnant or breastfeeding
• Patients who have known active Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection
• Patients who have active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization
• Patients unable to comply with the study and follow-up procedures
• Patients with history of cerebrovascular accident (CVA), myocardial infarction, clinically significant arrhythmia, unstable angina, pulmonary embolism, clinically significant deep vein thrombosis, gastrointestinal hemorrhage, clinically significant intestinal obstruction or perforation, or active uncontrolled bleeding within the previous 6 months before starting therapy
• Patients with a history of valvular heart disease (including valve replacement), known atrioventricular (A-V) malformation or evidence or history of septal aneurysm, other heart aneurysm, or any aneurysm of the major vessels
• Patients with a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Patients who have a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Patients who have received a live vaccine within 30 days before the first dose of study treatment
• Patients who have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids (patients receiving anticonvulsants are eligible)
• Patients who have primary central nervous system (CNS) tumors
• Patients with active known or suspected autoimmune disease or any illness that could compromise the immune system (e.g., prior organ transplant) within the past 2 years, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo, alopecia, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring chronic, and systemic immunosuppressive treatment within the past 2 years, not expected to recur in the absence of an external trigger, are permitted to enroll. Patients with inflammatory bowel disease and autoimmune related uveitis are not eligible
• Patients being treated with therapeutic doses of anticoagulants or antiplatelet agents (1 mg/kg of enoxaparin, 30 0mg of aspirin daily, 300 mg of clopidogrel daily or equivalent) within 7 days prior to first dose of SAR439459. Prophylactic use of anticoagulants or antiplatelets are allowed
• Prior treatment with any anti-transforming growth factor beta (TGFb) inhibitors
• Patients who received prior immunotherapy who developed toxicity leading to a permanent discontinuation of immunotherapy

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Timothy A Yap

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: November 30, 2020
• First Posted: January 28, 2021
• Study Start: February 9, 2021
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

US (1)