Nelmastobart in Combination With Trifluridine/ Tipiracil and Bevacizumab in Metastatic/ Recurrent Colorectal Cancer

NCT06873763 | Recruiting Phase 1 DMC

• 1 other identifier: STCUBE-003
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 5

Brief Summary

The objective of this multi-center, single-group, open-label Phase Ib/II study is to evaluate the safety, pharmacokinetics, and efficacy of nelmastobart in combination with trifluridine/tipiracil and bevacizumab in metastatic or recurrent colorectal cancer patients with resistance or intolerance to oxaliplatin- and irinotecan-based chemotherapy, and to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and the efficacy and safety of the combination therapy in BTN1A1-positive patients.

Conditions

Metastatic Colorectal Cancer (CRC); Recurrent Colorectal Cancer

Outcome Measures

Primary Outcomes (4)

• Incidence of DLT

  Status of DLT will be presented with frequency, percentage and its 95% confidence interval (CI).

  up to 6 months

• RP2D(Recommended Phase 2 Dose)

  The recommended phase 2 dose (RP2D) of nelmastobart in combination with trifluridine/tipiracil and bevacizumab

  up to 2 years

• MTD(Maximum Tolerated Dose)

  To find the maximum tolerated dose (MTD)

  up to 2 years

• Progression Free Survival (PFS) rate

  Time from the start of treatment to objective tumor progression or all-cause death will be presented with survival curve, median survival time and its 95% CI using the Kaplan-Meier estimation.

  up to 2 years

Secondary Outcomes (8)

• Phase 2 study; Overall Survival (OS)

  up to 2 years

• Phase 2 study; Objective Response Rate (ORR)

  up to 2 years

• Maximum plasma concentration (Cmax)

  up to 6 months

• Phase 2 study; Disease Control Rate (DCR)

  up to 2 years

• PFS(Progression free survival)

  up to 2 years

Study Arms (1)

Nelmastobart 800 mg+Trifluridine/Tipiracil+Bevacizumab

EXPERIMENTAL

3 reducing doses of Trifluridine/Tipiracil will be administered to participants

Drug: Nelmastobart 800 mg+Trifluridine/Tipiracil+ Bevacizumab

Interventions

Nelmastobart 800 mg+Trifluridine/Tipiracil+ Bevacizumab DRUG

Trifluridine/tipiracil is dose-deescalated from 35 mg/m² to 30 mg/m² and 25 mg/m² to determine the RP2D, in combination with fixed doses of Nelmastobart and Bevacizumab, in patients with metastatic colorectal cancer who are refractory or intolerant to prior oxaliplatin- and irinotecan-based chemotherapy.

Nelmastobart 800 mg+Trifluridine/Tipiracil+Bevacizumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥19 years old at the time of written informed consent
• Patients with histologically/cytologically confirmed metastatic/recurrent colorectal cancer after failure of, or not eligible for oxaliplatin and irinotecan-based standard anticancer therapy (If a subject had a radical surgery for colorectal cancer followed by adjuvant anticancer therapy, and the disease recurred during the adjuvant anticancer therapy or within 6 months from the end of the adjuvant anticancer therapy, the adjuvant anticancer therapy will be considered primary palliative therapy.)
• Subjects with at least one evaluable lesion, or non-measurable but evaluable lesion according to RECIST v1.1
• Subjects with ECOG performance status 0-1
• Subjects with adequate bone marrow and body organ functions
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Hemoglobin count (Hgb) ≥ 9.0 g/dL
• Platelet count ≥ 100 x 109/L
• Serum creatinine ≤ ULN x 1.5 or serum creatinine clearance \> 30mL/min
• Total bilirubin ≤ 1.5 x ULN (Subjects with biliary obstruction may be enrolled if they meet the criterion after adequate biliary drainage.)
• AST and ALT ≤ 3 x ULN in the absence of liver metastasis; or AST and ALT ≤ 5 x ULN in the presence of liver metastasis
• Subjects with adequate cardiac function at the screening visit
• QTc calculated using the Fredericia formula ≤ 480 msec (Those with QTc \>480 msec may be enrolled if the mean of 3 consecutive QTc measurements is \<480 msec.)
• A negative serum β-HCG test within 14 days prior to IP dosing for women of childbearing potential
• Subjects who agree, and are able to use during the study medically reliable methods of contraception as follows

You may not qualify if:

• Patients who have hypersensitivity to the active ingredient of IP or any of its components (excipients)
• Individuals who had cytotoxic chemotherapy within 14 days prior to randomization; treatment with IP in another clinical trial with the elapse of ≤2 weeks from the last dose of that IP or ≤5 folds the half-life of that IP; or treatment with monoclonal antibody therapy within the past 4 weeks
• Uncontrolled serious infection
• Confirmed PD during treatment with trifluridine/tipiracil for palliative care or confirmed recurrence within 6 months after the end of such treatment
• Individuals requiring high-dose steroids (\>10 mg/day prednisone or equivalent) or other immunosuppressants
• However, these individuals may be enrolled in the following cases.
• Short-term (\<7 days) use of systemic corticosteroids that are considered standard of care will be allowed.
• Subjects requiring intermittent use of bronchodilators, inhalant steroids, or local steroid injections will be allowed.
• Replacement therapy (e.g., thyroxine, insulin, physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered as a type of systemic treatment and will be allowed.
• Pregnant or lactating women
• Individuals with a history of autoimmune disease requiring systemic treatment (i.e., use of disease modifying therapy, corticosteroids, or immunosuppressants) within 2 years prior to the screening visit (However, enrollment will be possible for subjects with vitiligo, psoriasis not requiring systemic treatment, type 1 diabetes mellitus, hypothyroidism stably managed with hormone replacement therapy, Sjogren's syndrome, or resolved pediatric asthma/atopy.)
• Individuals with active central nervous system lesions (radiologically unstable or symptomatic brain lesions). With the exception of patients with meningeal metastasis, individuals who had radiotherapy or surgical treatment may be enrolled if there is evidence that the patient's condition is maintained without steroid therapy and that the disease of the brain lesion has not progressed for ≥4 weeks.
• Individuals with a documented history of cerebrovascular events (stroke or transient ischemic attack), unstable angina pectoris, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to the screening visit
• Patients with hypertensive encephalopathy or hypertension that is not adequately controlled with antihypertensives
• Individuals with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonia; or with active pneumonia based on screening chest X-rays

Sponsors & Collaborators

• STCube, Inc.: lead

Study Sites (5)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

NOT YET RECRUITING

Seoul National University Hospital

Seoul, KR, 03080, South Korea

NOT YET RECRUITING

Severance Hospital

Seoul, KR, 03722, South Korea

NOT YET RECRUITING

Asan Medical Center

Seoul, KR, 05505, South Korea

NOT YET RECRUITING

Korea University Anam Hospital

Seoul, 02841, South Korea

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Trifluridine

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

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Hyunju Yoo

CONTACT

+8225513370; ID@stcube.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: March 13, 2025
• Study Start: June 9, 2025
• Primary Completion: December 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5)