Neoadjuvant Dupilumab and Toripalimab in MSS CRC Subjects With Resectable Liver Metastases

NCT07277322 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY-25-01112PRMC-25-088 IIT
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1b/2 trial will evaluate the safety and efficacy of neoadjuvant immunotherapy in microsatellite stable (MSS) colorectal cancer (CRC) subjects with resectable liver metastases.

Conditions

Metastatic Colorectal Cancer; Liver Metastases

Keywords

Colorectal cancer; Liver metastases; Neoadjuvant immunotherapy; Dupilumab; Toripalimab; microsatellite stable

Outcome Measures

Primary Outcomes (1)

• Number of dose limiting toxicities (DLTs)

  Phase 2: Safety of treatment, defined as the frequency and percentage of DLTs, from start of treatment up to 30 days post the last administration of study drug (dupilumab).

  up to 30 days post last administration of study drug dupilumab

Secondary Outcomes (5)

• Major pathological response (MPR)

  Day of Surgery (day 16-22)

• Time to surgery

  up to 22 days

• Percentage of participants with adverse event

  within 90 days following the final dose of dupilumab

• Event free survival (EFS)

  Initial treatment to progression of disease, recurrence of tumor following surgery, up to 8 weeks, whichever comes first after first dose of dupilumab,

• Overall survival (OS)

  From treatment initiation until death from any cause, up to 2 years, whichever comes first

Study Arms (1)

Dupilumab and toripalimab

EXPERIMENTAL

Participants will receive the combination of Dupilumab and Toripalimab

Drug: Dupilumab; Drug: Toripalimab

Interventions

Dupilumab DRUG

Dupilumab is commercially sourced, and provided as 300mg pre-filled syringes, though packaging may vary. Dupilumab 600mg SC on Day 1 and 300mg SC on Day 15 (+/-2 days).

Dupilumab and toripalimab

Toripalimab DRUG

Toripalimab will be supplied as a liquid in sterile, single-use vials that will display the product lot number on the label. Each vial contains 240 mg/6 mL (40 mg/mL) solution. Toripalimab 240mg IV over 60 minutes or longer on Day 1 before planned surgery.

Dupilumab and toripalimab

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis of non-MSI-H/pMMR CRC
• Subjects who have biology-proven non-MSI-H/pMMR CRC and with radiographic findings suggestive of liver metastases may be eligible.
• Resectable liver metastases including:
• synchronous liver metastases (present at the time of diagnosis of MSS CRC) and treatment-naïve
• metachronous liver metastasis (developed after resection of the primary tumor) without prior adjuvant chemotherapy
• metachronous liver metastasis (developed after resection of the primary tumor) with adjuvant chemotherapy completed greater than 3 months from the time of consent.
• Surgical candidate for resection
• Age ≥ 18 years. Rationale: Because no dosing or adverse event data are currently available on the use of dupilumab in combination with toripalimab in subjects \<18 years of age, children are excluded from this study.
• ECOG Performance Status 0-1 (Karnofsky ≥60%,)
• Subjects with performance status \>1 carrying long-term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy may be enrolled at the investigator's discretion
• Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception upon study entry, for the duration of study participation, and for 3 months following completion of therapy.
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent. Legally authorized representatives may sign and give informed consent on behalf of study participants.

You may not qualify if:

• History of autoimmune disorder with the following exceptions:
• Vitiligo, alopecia, psoriasis or any chronic skin condition that does not require systemic therapy
• Hypothyroidism (e.g. following autoimmune thyroiditis) stable on thyroid replacement
• Celiac disease controlled by diet alone
• Treatment, for any reason, with an immunomodulatory drug, within 8 weeks from time of consent.
• Prior treatment with dupilumab within the last 8 weeks.
• Prior treatment with chemotherapy for MSS CRC or locoregional therapy to the target lesion (that will be biopsied and subsequently resected) within 3 months prior to entering the study.
• Previous therapy for a different cancer (a different primary) is acceptable.
• Use of investigational agents for treatment of cancer.
• Subjects with extrahepatic metastases that are not amendable to resectable or locoregional therapy, for whom the intent of surgery would not be curative.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10 days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements, as determined the treating investigator.
• Pregnant or nursing women due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Breastfeeding should be discontinued prior to study enrollment.
• Has a diagnosis of primary 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.
• Chronic steroids equivalent to ≤ 10mg prednisone are permitted.

Sponsors & Collaborators

• Dan Feng: lead
• Coherus Oncology, Inc.: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (8)

• Fakih M, Sandhu J, Wang C, Kim J, Chen YJ, Lai L, Melstrom K, Kaiser A. Evaluation of Comparative Surveillance Strategies of Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen Levels in Patients With Resected Colorectal Cancer. JAMA Netw Open. 2022 Mar 1;5(3):e221093. doi: 10.1001/jamanetworkopen.2022.1093.

  PMID: 35258578 BACKGROUND

• Pellini B, Chaudhuri AA. Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent. J Clin Oncol. 2022 Feb 20;40(6):567-575. doi: 10.1200/JCO.21.01929. Epub 2022 Jan 5.

  PMID: 34985936 BACKGROUND

• Brown B. How a hobby farm taught me to set priorities in academia. Nature. 2022 Oct 5. doi: 10.1038/d41586-022-03184-8. Online ahead of print. No abstract available.

  PMID: 36198820 BACKGROUND

• Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, Shabafrouz K, Ribi C, Cairoli A, Guex-Crosier Y, Kuntzer T, Michielin O, Peters S, Coukos G, Spertini F, Thompson JA, Obeid M. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019 Sep;16(9):563-580. doi: 10.1038/s41571-019-0218-0.

  PMID: 31092901 BACKGROUND

• Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, Manne S, Kraya AA, Wubbenhorst B, Dorfman L, D'Andrea K, Wenz BM, Liu S, Chilukuri L, Kozlov A, Carberry M, Giles L, Kier MW, Quagliarello F, McGettigan S, Kreider K, Annamalai L, Zhao Q, Mogg R, Xu W, Blumenschein WM, Yearley JH, Linette GP, Amaravadi RK, Schuchter LM, Herati RS, Bengsch B, Nathanson KL, Farwell MD, Karakousis GC, Wherry EJ, Mitchell TC. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med. 2019 Mar;25(3):454-461. doi: 10.1038/s41591-019-0357-y. Epub 2019 Feb 25.

  PMID: 30804515 BACKGROUND

• Barany F. [News about Crohn disease]. Lakartidningen. 1982 Feb 17;79(7):489-94. No abstract available. Swedish.

  PMID: 7087618 BACKGROUND

• Ivanova A, Qaqish BF, Schell MJ. Continuous toxicity monitoring in phase II trials in oncology. Biometrics. 2005 Jun;61(2):540-5. doi: 10.1111/j.1541-0420.2005.00311.x.

  PMID: 16011702 BACKGROUND

• Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018 Jan 5;359(6371):104-108. doi: 10.1126/science.aao3290.

  PMID: 29302014 BACKGROUND

Related Links

• Frank EH. Regression modeling strategies with applications to linear models, logistic and ordinal regression, and survival analysis. Springer; 2015.

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

dupilumab; toripalimab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Dan Feng, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Thomas Marron, MD, PhD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Central Study Contacts

Lisa Fitzgerald

CONTACT

(917) 748-0962; lisa.fitzgerald@mssm.edu

Rashmi Unawane

CONTACT

(212) 824-2385; rashmi.unawane@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Safety run-in phase of at most 6 subjects, guided by a 3+3 design. Phase 2: After enrolling 12 patients in the first stage, the trial will be terminated if no radiological responses are observed. If at least one response is observed, 9 additional patients will be enrolled for a total of 21. If 3 or more radiological responses are observed in the full cohort, the null hypothesis will be rejected and the treatment considered for further study.

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: December 11, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)