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Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC

ConditionMetastatic Microsatellite Stable Colorectal Carcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDan Feng

About this trial

Phase 1b/2 open-label study evaluates the safety, tolerability, and efficacy of combination immunotherapy with nadunolimab (anti-IL-1RAP) and toripalimab (anti-PD-1) in patients with chemotherapy-refractory metastatic microsatellite stable (MSS) colorectal cancer. Phase 1b will assess dose-limiting toxicity (DLT), while Phase 2 will evaluate objective response rate (ORR), including progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR). Exploratory analyses will investigate immunomodulatory effects through tumor and peripheral blood studies, and treatment will continue every 3 weeks for up to 1 year or until disease progression.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have a pathologically confirmed diagnosis of non-MSI-H/pMMR CRC.

Patients must have progressed (clinically or radiographically) on or after standard chemotherapy, including fluoropyrimidines, oxaliplatin, and irinotecan, or are intolerant to standard chemotherapy. Patients may have received, if eligible, anti-VEGF or anti-EGFR antibodies in combination with chemotherapy.

Patients must have at least 1 measurable target lesion at baseline ≥ 10mm in the longest diameter.

Patient must be willing and able to provide blood samples (6 heparinized, and two streck tubes, roughly 70 - 80 mL) at the time points indicated in the Study Calendar.

Disqualifiers

Patients who have had chemotherapy within 14 days from start of therapy.

Palliative radiotherapy is permitted at anytime, if deemed in the best interest of the patient.

Patients may not be receiving any other investigational agents.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring antibiotics (exception is a brief (≤10days) 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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Nadunolimab

    Drug

    5 mg/kg intravenously (IV) every 3 weeks (Q3W)

  • Toripalimab

    Drug

    240 mg IV every 3 weeks (Q3W)

Treatment groups

24 Participants
are divided into 1 treatment group
Group A: Nadunolimab and ToripalimabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Dose-Limiting Toxicities (DLTs)

For the Phase 1b portion, Dose-Limiting Toxicities (DLTs) will be assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Adverse events are graded on a scale from 1 (mild) to 5 (death related to AE). Permanent discontinuation of study treatment will occur for any severe (Grade 3) drug-related adverse event that recurs or for any life-threatening (Grade 4) event.

Time frame
The first cycle (day1 - day21) constitutes the DLT window.
2

Objective Response Rate (ORR)

For the phase 2 portion, ORR will be assessed based on the definition, as the combined percent of the subjects experiencing a partial response (PR) or a complete response (CR) at anytime within the first year from the initiation of therapy, or until the documented progression of disease or start of a new anti-cancer therapy. Radiographic response will be determined by the RECIST v1.1

Time frame
Treatment initiation through 12 months, or until documented disease progression or initiation of new anti-cancer therapy, whichever occurs first

Secondary outcomes

1

Progression-free Survival (PFS)

Progression-free survival (PFS) is defined as the time in days from the first administration of nadunolimab until documented progression of disease on imaging or death.

Time frame
From first dose through disease progression, death, or up to 12 months, whichever occurs first.
2

Overall survival (OS)

Overall survival (OS) is defined as the time in days from the first administration of nadunolimab until documented death from any cause.

Time frame
From first administration of nadunolimab until documented death from any cause, or up to 12 months, whichever occurs first.
3

Disease control rate (DCR)

Disease control rate (DCR) is defined as the percent of the subjects experiencing a best objective response of PR, CR or stable disease (SD).

Time frame
From first administration of nadunolimab until best objective response, or up to 12 months, whichever occurs first.
4

Duration of response (DOR)

Duration of response (DOR) is defined as the time from which a subject achieves either a PR or a CR until subsequent progression of disease is documented radiographically or clinically.

Time frame
up to 12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Dan Feng

Lead sponsor

Icahn School of Medicine at Mount Sinai

Sponsor institution

Coherus Oncology, Inc.

Collaborator

Cantargia AB

Collaborator

Source ClinicalTrials.gov
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