A Randomized, Double-Blind, Phase 3 Study of Standard-of-Care Chemotherapy and Bevacizumab With or Without INCA33890 in the First-Line Treatment of Metastatic Microsatellite Stable Colorectal Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Incyte Corporation

External identifiers

EU CT number

2025-523735-19-00

ClinicalTrials.gov

NCT07284849

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To evaluate the efficacy of the combination of INCA33890 and SOC therapy versus placebo and SOC therapy.

Secondary objectives 4

1. To further evaluate the efficacy of the combination of INCA33890 and SOC therapy versus placebo and SOC therapy in the Overall Population.
2. To further evaluate the efficacy of the combination of INCA33890 and SOC therapy versus placebo and SOC therapy.
3. To evaluate the safety and tolerability of the combination of INCA33890 and SOC therapy versus placebo and SOC therapy.
4. To evaluate changes from baseline in health-related quality of life assessments.

Conditions and MedDRA coding

Metastatic Microsatellite Stable Colorectal Cancer

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Ability to comprehend and willingness to sign a written ICF for the study.
2. Aged 18 years or older, inclusive, at the time of signing the ICF.
3. Histologically or cytologically confirmed metastatic colorectal adenocarcinoma (Stage IV per the American Joint Committee on Cancer, Cancer Staging Manual, 8th Edition) not amenable to curative resection.
4. No prior systemic treatment for unresectable or metastatic CRC. Participants who previously received neoadjuvant and/or adjuvant therapy are allowed to enroll if there was no recurrence of disease within 12 months of last systemic therapy administration.
5. Radiographically measurable disease (based on local site investigator/radiology evaluation) per RECIST v1.1 criteria.
6. Adequate organ function as defined in the protocol
7. Willingness to avoid pregnancy or fathering children.

Exclusion criteria 18

1. Cancer History: Known MSI-H/dMMR status per local standard of practice as obtained from historical data in the participant's medical record.
2. BRAF V600E mutation as obtained from historical data in the participant's medical record.
3. History of other malignancy within 2 years of study entry.
4. Untreated and/or progressing CNS metastases (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).
5. Tumor known to invade or encase a major blood vessel or any history of clinically significant bleeding from tumor lesions within 30 days before enrollment.
6. Treatment with an anti–PD-(L)1 or anti–CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways, for any indication within the past 3 years.
7. Toxicity from prior therapy that has not recovered to ≤ Grade 1 or baseline. Paresthesia and/or peripheral sensory neuropathy of Grade 2 or higher due to prior chemotherapy (eg, oxaliplatin) are exclusionary.
8. Concurrent anticancer therapy other than the therapies being tested in this study.
9. Received thoracic radiation of > 30 Gy within 6 months of the first dose of study treatment.
10. Medical History: History of organ transplant, including allogeneic stem cell transplantation.
11. Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed.
12. Significant concurrent and/or uncontrolled medical condition as detailed in the protocol
13. Uncontrolled active HBV or HCV infection.
14. HIV positive, unless all of the following criteria are met: a. CD4+ count ≥ 350 μL. b. Undetectable viral load. c. Receiving highly active antiretroviral therapy.
15. Medications: 19. Current use of chronic systemic corticosteroids (ie, > 10 mg/day of prednisone or equivalent).
16. Received a live vaccine within 28 days before the first dose of study treatment.
17. Current use of prohibited medication as defined in the protocol.
18. Known complete DPD deficiency as reported in the participant's medical record. Local guidelines and regulations for DPD activity testing and dose adjustments should be applied in case of partial deficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS, defined as the time from the date of randomization to the date of the first documented progression as determined by BICR (Blinded Independent Central Review) per RECIST v1.1 or death due to any cause.

Secondary endpoints 4

1. OS, defined as the time from the date of randomization to the date of death due to any cause.
2. Objective response, defined as CR or PR as determined by BICR (Blinded Independent Central Review) per RECIST v1.1.
3. DOR, defined as the time from the earliest date of documented response until the earliest date of disease progression as determined by BICR per RECIST v1.1 or death due to any cause, whichever occurs first.
4. TEAEs per CTCAE v6.0 and TEAEs leading to dose interruption or study drug discontinuation.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Third parties 8

Locations

10 EU/EEA countries · 76 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 100 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications