Regorafenib With Tislelizumab in Patients With Selected Mismatch Repair-Proficient/Microsatellite Stable Cancers

NCT05582031 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: TRIO042
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

REFIT-MSS is a non-randomized, multicenter, open-label, multi-cohort, 2-stage, phase II trial to evaluate the efficacy and safety of regorafenib in combination with tislelizumab (referred as Rego-Tisle) in adult patients with select advance, previously treated, Mismatch Repair-Proficient/Microsatellite (pMMR/MSS) stable solid cancers. The multi-cohort design will allow for the examination of 8 separate cohorts of different cancers to determine whether further examination may be warranted in the individual indications.

Conditions

Anal Squamous Cell Carcinoma; Colorectal Neoplasms; Soft Tissue Sarcoma; Malignant Pleural Mesothelioma; Small Cell Lung Carcinoma; Castrate Resistant Prostate Cancer; Neuroendocrine Carcinoma of Prostate; Gastroenteropancreatic Neuroendocrine Neoplasm

Keywords

pMMR; MSS; Advanced solid tumors; MKI; PD-1 inhibitors

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival at 6 months (PFS-6) as per Investigator Assessment

  PFS-6 is defined as the proportion of patients who remained free of PFS event (disease progression or death) at 6 months from the date of enrollment.

  6 Months

Secondary Outcomes (7)

• Overall Response Rate

  24 Months

• Disease Control Rate (DCR)

  24 Months

• Duration of Response (DOR)

  24 Months

• Growth Modulation Index (GMI)

  24 Months

• Overall Survival (OS)

  12 Months

Study Arms (1)

Regorafenib 90 mg + Tislelizumab 300 mg (Rego-Tisle)

EXPERIMENTAL

The trial will include 8 cohorts of patients, with each cohort considered as a single-arm; all patients enrolled will be treated with regorafenib at a dose of 90 mg orally once daily, on days 1 to 21 of a 28 cycle in combination with tislelizumab 300 mg intravenously day 1 (of a 28 day cycle).

Combination Product: Regorafenib in combination with Tislelizumab

Interventions

Regorafenib in combination with Tislelizumab COMBINATION_PRODUCT

Regorafenib 30 mg/tablet + Tislelizumab 100 mg/10 ml vial

Regorafenib 90 mg + Tislelizumab 300 mg (Rego-Tisle)

Eligibility Criteria

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

You may qualify if:

• Signed and dated PICF obtained prior to any trial-specific procedure that is not part of standard patient care.
• Patient is ≥ 18 years-old at the time of PICF signature (or the legal age of consent in the jurisdiction in which the trial is taking place).
• Histologically or cytologically confirmed solid tumor belonging to one of the cohorts specified in the protocol. To be eligible, patient must meet the criteria for tumor type, stage and prior anti-cancer therapy according to the protocol.
• Tumor must be:
• In all colorectal (CRC patients) and in any non-CRC patient with dMMR/MSI testing available prior to enrollment: pMMR/MSS tumor based on IHC, MSI-PCR or NGS testing, as performed at the site prior to enrollment according to site's standard practice.
• In any non-CRC patient with unknown dMMR/MSI status: the site must confirm at screening that the patient has available and retrievable archival tumor tissue from the primary or metastatic site, for submission to a central laboratory for dMMR/MSI testing.
• Measurable disease by CT or MRI per Response Evaluation Criteria in Solid Tumors (version 1.1), based on tumor assessment performed within 28 days of enrollment.
• Progressive cancer at the time of trial entry based on clinical or radiographic findings or tumor marker evaluation, according to Investigator's judgment, or cancer that is not amenable to standard therapies even if not progressing.
• ECOG Performance Scale score of 0 or 1 at enrollment.
• Adequate hematologic and organ function as assessed by the following laboratory tests, performed at screening (specified within the protocol).
• Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
• Women of childbearing potential (CBP) must have confirmed negative serum pregnancy test (for β-hCG) within 7 days prior to enrollment.
• Women of CBP must agree to remain completely abstinent (complete avoidance of heterosexual intercourse) or use highly effective contraceptive methods (i.e., with a failure rate of \< 1% per year) during the Treatment Phase and for at least 7 months after the last trial treatment intervention.
• Men who are sexually active with women of CBP must agree to remain completely abstinent (complete avoidance of heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm during the Treatment Phase and for a total of 7 months post-treatment completion.

You may not qualify if:

• Prior treatment with regorafenib.
• Prior treatment with a PD1, PD-L1/PD-L2, or CTLA-4 inhibitor, or any other drug or antibody targeting T-cell co-stimulation or checkpoint pathways, except in patients that meet all the following criteria:
• Patient received a PD1, PD-L1/PD-L2, or CTLA-4 inhibitor, or any other drug or antibody targeting T-cell co-stimulation or checkpoint pathways in either:
• Neoadjuvant and/or adjuvant setting and had no relapse within 12 months of completing immunotherapy
• Advanced disease setting and had no progression during immunotherapy
• Patient tolerated immunotherapy and did not need to discontinue treatment due to intolerable toxicity
• Evidence of progressive or symptomatic CNS metastases. Patients with treated CNS metastases are eligible if they meet all the following criteria:
• Minimal neurologic symptoms
• Evidence of stable disease (for at least 2 weeks prior to enrollment) or response on a follow-up scan performed after CNS treatment completion
• Require corticosteroids at a dose ≤ 10 mg daily of prednisone or equivalent
• Previous treatment with live vaccine within 28 days of planned start of trial drugs (seasonal flu vaccines that do not contain a live virus are permitted).
• Concurrent participation in another clinical study, unless it is: (a) an observational (noninterventional) study, or (b) the follow-up period of an interventional trial and patient did not receive an investigational agent/device within 28 days before enrollment (or within 5 half-lives of the drug).
• Major surgical procedure, open biopsy, significant traumatic injury, radiation therapy and/or systemic anti-cancer therapy ≤28 days prior to enrollment. Patients must have recovered adequately from the toxicity and/or complications from these interventions before enrollment. Radiation therapy given with palliative intent is allowable if finalized ≥ 14 days prior to enrollment.
• Known hypersensitivity to any of the trial drugs or its formulation components.
• Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids.

Sponsors & Collaborators

• Translational Research in Oncology: lead
• Bayer: collaborator
• Novartis: collaborator

MeSH Terms

Conditions

Anus Neoplasms; Colorectal Neoplasms; Sarcoma; Mesothelioma, Malignant; Small Cell Lung Carcinoma

Interventions

regorafenib; tislelizumab

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Colonic Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Josep Tabernero

  Medical Oncology Department, Vall d'Hebron Institute of Oncology, CIBERONC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The trial will include 8 cohorts of patients. Each cohort is considered as a single-arm activity-estimating sub-study with PFS-6 as the primary endpoint. A strong primary endpoint signal seen in a cohort may allow for expansion of the cohort, independently of the status of the other cohorts. Similarly, a cohort may be opened and/or closed for enrollment independently of others.

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 17, 2022
• Study Start: April 30, 2023
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: June 7, 2023

Record last verified: 2023-06