A 3-Arm, Randomized, Blinded, Active-Controlled, Phase II Study of RO7121661, a PD1-TIM3 Bispecific Antibody and RO7247669, a PD1-LAG3 Bispecific Antibody, Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus

  • STATUS
    Recruiting
  • End date
    May 31, 2025
  • participants needed
    210
  • sponsor
    Hoffmann-La Roche
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Updated on 12 October 2022
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Summary

This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab, in patients with advanced or metastatic esophageal squamous-cell carcinoma (ESCC) refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen.

Following approval of the protocol amendment version 3, recruitment into the RO7121661 arm has been stopped. The decision to stop recruitment for RO7121661 was based on strategic considerations and not based on emerging safety and/or efficacy data. The benefit/risk assessment for RO7121661 remains unchanged.

The study was planned to enroll participants randomized in a 1:1:1 ratio to receive RO7121661, RO7247669, or nivolumab. With version 3 of the protocol, recruitment into the RO7121661 has stopped, and moving forward, participants will be randomized in a 1:1 ratio to receive either RO7247669 or nivolumab.

Details
Condition Advanced or Metastatic Esophageal Squamous Cell Carcinoma
Treatment Nivolumab, RO7121661, RO7247669
Clinical Study IdentifierNCT04785820
SponsorHoffmann-La Roche
Last Modified on12 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Advanced or metastatic, histologically confirmed esophageal squamous-cell carcinoma (ESCC)
Patients who have previously received 1 line of treatment with either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in non-curative intention prior to randomization; or patients who received treatment with a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had recurrence or progression within 24 weeks after the last dose of the treatment
Radiologically measurable disease according to RECIST v1.1. Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
A life expectancy of at least (≥)12 weeks
Tissue samples must be provided for analysis of anti-programmed death ligand-1 (PD-L1) tumor positivity
Adverse events from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade ≤1, except alopecia (any grade), vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy
Adequate cardiovascular, hematological, liver, and renal function
Serum albumin ≥25 grams per liter (g/L)
For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and activated partial thromboplastin time ≤1.5 times (×) the upper limit of normal (ULN); for participants receiving therapeutic anticoagulation: stable anticoagulant regimen
A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods during the treatment period and for at least 5 months after the final dose of study drug and have a negative pregnancy test (blood) within the 7 days prior to randomization
A male participant must remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom plus an additional contraceptive method and refrain from donating sperm during the treatment period and for at least 5 months after the final dose of study drug

Exclusion Criteria

Pregnancy, lactation, or breastfeeding
Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
Patients with significant malnutrition. Patients whose nutrition has been well controlled for ≥28 days prior to randomization may be enrolled
Evidence of complete esophageal obstruction not amenable to treatment
Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree). Patients with manageable fistula may be included at the Investigator's discretion
Symptomatic central nervous system (CNS) metastases
Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for ≥14 days prior to randomization
Active or history of carcinomatous meningitis/leptomeningeal disease
Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or enzyme inducing anticonvulsants in the last 28 days prior to randomization
Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry
Active second malignancy (with some exceptions)
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.)
Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization
Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization
Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease
Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
Dementia or altered mental status that would prohibit informed consent
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently)
Active or history of autoimmune disease or immune deficiency
Positive human immunodeficiency virus (HIV) test at screening
Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test at screening
Positive hepatitis C virus (HCV) antibody test at screening
Prior cancer therapy with any immunomodulatory agents including checkpoint inhibitors (CPIs; such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3)
Vaccination with live vaccines within 28 days prior to randomization, or anticipation that a live attenuated vaccine will be required during the study
Treatment with therapeutic oral or IV antibiotics within 14 days prior to randomization
Concurrent therapy with any other investigational drug (defined as treatment for which there is currently no regulatory authority approved indication) 28 days or 5 half-lives of the drug (whichever is shorter) prior to randomization
Treatment with immune-modulating and immune suppressive agents/medication 5 half-lives or 28 days (whichever is shorter) prior to randomization
Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease)
Radiotherapy within the last 28 days before start of study drug treatment is not allowed, with the exception of limited palliative radiotherapy
Prior treatment with adoptive cell therapies, such as chimeric antigen receptor T cells (CAR-T) therapies
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