A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors
REGOMUNE
2 other identifiers
interventional
747
1 country
7
Brief Summary
Assessment of the efficacy and safety of Regorafenib and Avelumab in patients with advanced or metastatic solid tumors (ten cohorts), once the Recommanded Phase II Dose (RP2D) has been determined (phase I trial). Assessement of the efficacy and safety of a low-dose of regorafenib (80mg/day) with avelumab in patients with advanced or metastatic colorectal tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2018
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 20, 2018
CompletedFirst Posted
Study publicly available on registry
March 23, 2018
CompletedStudy Start
First participant enrolled
May 4, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2025
CompletedMarch 3, 2023
March 1, 2023
6.7 years
February 20, 2018
March 2, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
PHASE I : Recommended phase II dose (RP2D)
Recommended phase II dose (RP2D) evaluated on the first cycle (Day 1 to Day 28) of regorafenib when prescribed in association with avelumab.
During the first cycle (28 days)
PHASE II (7cohorts A, C, D, E, F and G) : Assessment of the antitumor activity of regorafenib
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab based on objective response under treatment defined as CR or PR following RECIST v1.1 criteria.
Throughout the treatment period, an average of 6 months
Phase II (cohorts B, H, I, M, N, O and P): Assessment of the antitumor activity of regorafenib
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab based on 6-month progression-free rate, defined as CR, PR and SD following RECIST v1.1 criteria.
6 months
Phase II (cohort A'): Assessment of the antitumor activity of regorafenib
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab based on 4-months progression-free rate, defined as CR, PR and SD following RECIST v1.1 criteria.
4 months
Secondary Outcomes (33)
PHASE I : Maximum Tolerated Dose (MTD)
During the first cycle (28 days)
PHASE I : Dose Limiting Toxicities (DLT)
During the first cycle (28 days)
PHASE I : Toxicity
Throughout the treatment period, an average of 6 months
PHASE I : Assessment of the antitumor activity of regorafenib - Best overall response
Throughout the treatment period, an average of 6 months
PHASE I :Assessment of the antitumor activity of regorafenib - objective response rate under treatment
Throughout the treatment period, an average of 6 months
- +28 more secondary outcomes
Study Arms (18)
Phase 1 : Regorafenib + Avelumab
EXPERIMENTALAvelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort A Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab + Regorafenib Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort B Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort C Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort D Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort E Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort F Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort G Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort H Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort I Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort A' Regorafenib low-dose + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort J Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort K Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort L Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort M Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort N Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort O Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Phase 2 : cohort P Regorafenib + Avelumab
EXPERIMENTALTreatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Interventions
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.). Patients will be allocated 3 dose levels of Regorafenib following a 3 + 3 design.
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.). Avelumab will be administered on cycle 1 Day 15 as a 1-hour intravenous (IV) infusion (10mg/kg), repeated every two weeks thereafter (ie. Day 1 and Day 15 of each subsequent cycle, as a 1-hour intravenous infusion).
Phase 2 : Regorafenib - All patients will be treated at the RP2D of regorafenib defined in the preliminary phase 1 trial with the same schedule as in the phase I.
Phase 2 : Avelumab - All patients will be treated with avelumab with the same schedule as in the phase 1 trial.
Phase 2 : Regorafenib - All patients will be treated at a fixed low-dose of regorafenib of 80 mg/day
Eligibility Criteria
You may qualify if:
- Histology:
- Dose escalation part: histologically confirmed non MSI-H or deficient-MMR colorectal cancer, or GIST, or esophageal or gastric carcinoma or hepatobiliary cancers,
- Phase II trials : histologically confirmed
- non MSI-H or deficient-MMR colorectal cancer (cohort A),
- or GIST (cohort B). As recommended diagnosis by INCa, patients with GIST must have histologically confirmed by central review, except if it has been already confirmed by the RRePS Network
- or esophageal or gastric carcinoma (cohort C),
- or hepatobiliary cancers (cohort D),
- or soft-tissue sarcoma (STS) (cohort E). As recommended diagnosis by INCa, patients with STS must have histologically confirmed by central review, except if it has been already confirmed by the RRePS Network
- or radioiodine-refractory differentiated thyroid cancer \[RR-DTC\] (cohort F),
- or neuroendocrine gastroenteropancreatic tumors grade 2 and 3
- or Non-small cell lung cancer (cohort H)
- or Solid tumors including soft-tissue sarcoma with immune signature (cohort I), i.e. presence of tertiary lymphoid structures on tumor sample as determined by central review.
- or urothelial cancer (cohort J)
- or HPV-associated cancer (cohort K) with molecular confirmation p16 positive status,
- triple negative breast cancer (cohort L)
- +43 more criteria
You may not qualify if:
- Previous treatment with Avelumab or Regorafenib,
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways), except for cohort H (NSCLC), Cohort I (Solid tumors (including Soft Tissue Sarcoma) with immune signature (TLS+)) and cohort P (malignant pleural mesothelioma),
- Evidence of progressive or symptomatic or newly diagnosed central nervous system (CNS) or leptomeningeal metastases,
- Men or women of childbearing potential who are not using an effective method of contraception as previously described;
- Participation to a study involving a medical or therapeutic intervention in the last 30 days,
- Previous enrolment in the present study,
- Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
- Known hypersensitivity to any involved study drug or of its formulation components,
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent :
- Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
- 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 or 10 mg equivalent prednisone per day
- Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment,
- Has known hepatitis B or hepatitis C, active and/or treated by antiviral therapy
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS),
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Institut Bergoniélead
- Bayercollaborator
- Merck KGaA, Darmstadt, Germanycollaborator
Study Sites (7)
Institut Bergonié
Bordeaux, 33076, France
Centre Hospitalier Régional Universitaire - CHU Morvan
Brest, 29200, France
Centre Léon Bérard
Lyon, 69008, France
Institut de Cancérologie de Montpellier
Montpellier, 34298, France
Institut Curie
Paris, 75248, France
IUCT Oncopôle - Institut Claudius Regaud
Toulouse, 31059, France
Institut Gustave Roussy
Villejuif, 94800, France
Related Publications (4)
Toulmonde M, Guegan JP, Spalato-Ceruso M, Valentin T, Bahleda R, Peyraud F, Rey C, Kind M, Cantarel C, Bellera C, Vanhersecke L, Bessede A, Italiano A. Reshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-angiogenics: a phase 2 trial of regorafenib combined with avelumab. Signal Transduct Target Ther. 2025 Jun 27;10(1):202. doi: 10.1038/s41392-025-02278-9.
PMID: 40579407DERIVEDCousin S, Guegan JP, Palmieri LJ, Metges JP, Pernot S, Bellera CA, Assenat E, Korakis I, Cassier PA, Hollebecque A, Cantarel C, Kind M, Soubeyran I, Sokol H, Vanhersecke L, Bessede A, Italiano A. Regorafenib plus avelumab in advanced gastroenteropancreatic neuroendocrine neoplasms: a phase 2 trial and correlative analysis. Nat Cancer. 2025 Apr;6(4):584-594. doi: 10.1038/s43018-025-00916-3. Epub 2025 Apr 9.
PMID: 40204996DERIVEDCousin S, Cantarel C, Guegan JP, Mazard T, Gomez-Roca C, Metges JP, Bellera C, Adenis A, Korakis I, Poureau PG, Bourcier K, Toulmonde M, Kind M, Rey C, Auzanneau C, Bessede A, Soubeyran I, Italiano A. Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. Eur J Cancer. 2022 Feb;162:161-169. doi: 10.1016/j.ejca.2021.11.012. Epub 2022 Jan 5.
PMID: 34998048DERIVEDToulmonde M, Brahmi M, Giraud A, Chakiba C, Bessede A, Kind M, Toulza E, Pulido M, Albert S, Guegan JP, Cousin S, Mathoulin-Pelissier S, Perret R, Croce S, Blay JY, Ray-Coquard I, Floquet A, Italiano A. Trabectedin plus Durvalumab in Patients with Advanced Pretreated Soft Tissue Sarcoma and Ovarian Carcinoma (TRAMUNE): An Open-Label, Multicenter Phase Ib Study. Clin Cancer Res. 2022 May 2;28(9):1765-1772. doi: 10.1158/1078-0432.CCR-21-2258.
PMID: 34965951DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 20, 2018
First Posted
March 23, 2018
Study Start
May 4, 2018
Primary Completion
December 31, 2024
Study Completion
December 31, 2025
Last Updated
March 3, 2023
Record last verified: 2023-03