Nelmastobart in Combination With Tas-102 and Bevacizumab in Recurrent/Metastatic Colorectal Cancer

A Single-arm, Open-label, Phase Ib Clinical Trial Evaluating the Safety, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of Nelmastobart in Combination With TAS-102 and Bevacizumab in Recurrent/Metastatic Colorectal Cancer

Nelmastobart（hSTC810） is a novel humanized monoclonal antibody that fuses on IgG4 and targets a novel immune checkpoint protein, BTN1A1+.This is an phase Ib bridging trial conducted in China to assess the safety, tolerability, and pharmacokinetic characteristics of Nelmastobart in combined with TAS-102 and Bevacizumab in Chinese participants with mCRC, and to verify that the safety results align with those from the Korean STCUBE-003 phase Ib trial. The phase Ib trial will also provide supportive data for conducting a randomized, double-blind, controlled Phase II study in China.

Study Overview

• Status: Not yet recruiting
• Conditions: Colonrectal Cancer (CRC)
• Intervention / Treatment: Drug: Nelmastobart in combination with TAS-102 and Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhang Jian, M.D; Phone Number: 0086-13911127863; Email: zhjian940105@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who participate in the study must meet all of the following inclusion criteria.

  1. Adults ≥18 years old and of any gender when signing the informed consent form.
  2. Participants with metastatic/recurrent colorectal cancer confirmed by histopathology/cytology who have not responded to or are unable to receive standard anti-cancer therapy based on oxaliplatin and irinotecan. Participants who undergo curative surgery for colorectal cancer and receive adjuvant anti-cancer therapy will be considered to have received their first palliative anti-cancer therapy if their disease recurs during or within 6 months after completion of the adjuvant anti-cancer treatment.
  3. According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, there must be at least one measurable or assessable lesion present.
  4. Participants with ECOG performance status 0-1

  5. Participants with adequate bone marrow and body organ functions

     1. Absolute neutrophil count (ANC) ≥ 2.0 x 109/L
     2. Hemoglobin count (Hgb) ≥ 9.0 g/dL
     3. Platelet count ≥ 100 x 109/L
     4. Serum creatinine ≤ ULN x 1.5 or serum creatinine clearance > 30mL/min
     5. Total bilirubin ≤ 1.5 x ULN (Participants with biliary obstruction may be enrolled if they meet the criterion after adequate biliary drainage.)
     6. AST and ALT ≤ 3 x ULN in the absence of liver metastasis;
     7. or AST and ALT ≤ 5 x ULN in the presence of liver metastasis
  6. Confirm that participants 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.).
  7. A negative serum β-HCG test within 14 days prior to IP dosing for women of childbearing potential

  8. Participants who agree, and are able to use during the study medically reliable methods of contraception as follows:

     To be eligible for enrollment, women of childbearing potential (all women who can have physiological pregnancy during IP treatment and for 6 months after the end of IP treatment unless they use appropriate methods of contraception) must use the following methods of contraception.

     1. Participants must refrain from any type of sexual intercourse, and persistent abstinence in daily life is recommended. Periodic abstinence (e.g., rhythm method, cervical mucus method, basal body temperature method, etc.) and withdrawal method are not acceptable methods of contraception.
     2. Female sterilization procedures: Bilateral ovariectomy with or without hysterectomy; tubal ligation within 6 weeks prior to enrollment in this study. If the subject is confirmed to have childbearing potential based on the assessment of hormone level, only bilateral ovariectomy will be permitted.
     3. Vasectomized partner (at least 6 months prior to screening). For women who participate in the study, the vasectomized partner must be the only partner during her participation in this study.
     4. Men must use condoms during sexual intercourse during and after IP treatment (for 6 months after the last IP dose).
  9. Life expectancy ≥3 months
  10. Participants who consent to sampling tumor tissues or collecting tumor tissue samples obtained within 2 years prior to the screening visit.
  11. Participants who, after being fully informed of the study, voluntarily decide to participate in the study, provide written informed consent, and agree to comply with study procedures during the study.

Exclusion Criteria:

• Participants who meet any of the following exclusion criteria will be excluded from the study.

  1. Participants who have hypersensitivity to the active ingredient of IP or any of its components (excipients)
  2. Participants 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
  3. Uncontrolled serious infection
  4. Confirmed PD during treatment with trifluridine/tipiracil for palliative care or confirmed recurrence within 6 months after the end of such treatment

  5. Participants requiring high-dose steroids (>10 mg/day prednisone or equivalent) or other immunosuppressants However, these participants may be enrolled in the following cases.

     1. Short-term (<7 days) use of systemic corticosteroids that are considered standard of care will be allowed.
     2. Participants requiring intermittent use of bronchodilators, inhalant steroids, or local steroid injections will be allowed.
     3. 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.
  6. Pregnant or lactating women
  7. Participants 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.)
  8. Participants 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.
  9. Participants 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
  10. Participants with hypertensive encephalopathy or hypertension that is not adequately controlled with antihypertensives
  11. Participants 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
  12. Participants who received allogeneic stem cell or solid organ transplants
  13. Participants who received live attenuated vaccines within 30 days prior to the screening visit. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/(varicella) zoster, yellow fever, rabies, bacillus Calmette-Guerin, and typhoid vaccines. Injectable seasonal influenza vaccines are generally killed virus vaccines and will be allowed. However, intranasal influenza vaccines are live attenuated vaccines and will not be allowed.

  14. Participants with a history of other primary cancers However, enrollment will be possible for the following cancers.

      1. Adequately treated skin cancer (basal cell or squamous carcinoma) that is not melanoma, superficial cervical cancer or stage 1 bladder cancer, completely resected thyroid cancer which did not metastasize and for which all treatment is completed (Scars must have been adequately treated prior to study enrollment).
      2. Treated solid tumor with no evidence of recurrent disease at least 36 months prior to screening
  15. Side effects of prior anticancer therapy that did not recover to Grade ≤1 (with the exception of alopecia)
  16. Participants who had radiotherapy in an extensive lesion involving ≥30 % of the bone marrow within 4 weeks prior to the screening visit or limited range radiotherapy for palliative care within 2 weeks
  17. Participants who had major surgery within 4 weeks prior to the screening visit or who have not recovered from side effects of surgery
  18. Participants who are unable to take drugs orally or who have a past history, or pathological findings of major gastrointestinal surgery that may affect the absorption of IP
  19. Participants who have evidence of active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) However, enrollment will be possible for the following cases.

  20. Participants with positive hepatitis B surface antigen (HBsAg) may be enrolled if HBV DNA is negative based on a local test.

      1. Participants with positive hepatitis B core antibody (IgG anti-HBc) and a history of HBV infection may be enrolled if HBV DNA is negative.
      2. Participants with positive anti-HCV Ab may be enrolled if HCV RNA is negative.
      3. Participants with hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
  21. Participants with medical, psychiatric, or cognitive disorders or impaired ability to understand information, provide prior consent, comply with protocol procedures, or complete the study
  22. Those whom the investigator deems inappropriate for participation in this clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nelmastobart in combination with TAS-102 and Bevacizumab for recurrent/metastatic CRC

Drug: Nelmastobart in combination with TAS-102 and Bevacizumab; Drug name: Nelmastobart. Specifications: 400 mg/8 ml. Formulation: Sterile concentrated solution for injection. Batch number: XXX. Manufactured and supplied by Samsung Biologics Co., Ltd. (SBL), on behalf of STCube, Inc.; Drug name: Qufluorodeoxyuridine/tipiracil. Specifications: 15mg, 20mg. Formulation: film-coated tablet. Batch number: XXX. Produced and supplied by Taiho Pharmaceutical Co., Ltd.; Drug name: Bevacizumab. Specifications: 100 mg, 400 mg. Formulation: concentrated solution for injection. Batch number: XXX. Produced and supplied by XXX Company. Experimental: Cohort (Phase 1b) Nelmastobart 800 mg + Tas102 35 mg/m² + Bevacizumab 5 mg/kg (Starting Dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLT	Definition of DLT: The severity of AEs observed during the trial was determined and recorded according to the NCI CTCAE v6.0 grading criteria. The DLT observation period spanned the first treatment cycle (i.e., from C1D1, the first administration, to C1D28).According to the definition of DLT, "drug-related" is defined as follows: an AE is considered to be related to the investigational product if, in the opinion of the investigator, the relationship is "definitely related," "likely related," or "possibly related."	up to 6 months
Permanent discontinuation of IP due to adverse drug reactions (ADRs)	The incidence and rate of permanent discontinuation of IP due to adverse drug reactions (ADRs)	up to 6 months
AEs(Adverse Events)	Status of AEs will be presented with frequency, percentage and its 95% CI. AEs will be classified by SOC and PT of MedDRA (latest version) and presented with frequency, percentage and its 95% CI.	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax)	Maximum plasma concentration of Nelmastobart to evaluate PK parameters for the first and the subsequent cycles.	up to 6 months
Objective response rate (ORR)	To evaluated by the Independent Review Committee (IRC) in accordance with the RECIST1.1 criteria.	up to 6 months
Immunogenicity indicators:	Incidence of antibody formation against drugs (ADA)	up to 6 months
Tmax(Time to Maximum Plasma Concentration)	Time to reach Tmax of Nelmastobart to evaluate the PK parameters for the first and the subsequent cycles.	up to 6 months
ORR assessed by researchers	ORR assessed primarily by researchers based on the RECIST1.1 criteria.	up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory evaluation indicators.	The level of BTN1A1 expression in the tumor tissue samples of the subjects	up to 6 months
ORR between different levels of BTN1A1	The difference in ORR between patients with positive and negative BTN1A1 results	up to 2 years
Efficacy vs. BTN1A1	The correlation between the expression levels of BTN1A1 and efficacy indicators	up to 2 years

Collaborators and Investigators

• Sponsor: STCube, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 12, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; trifluridine tipiracil drug combination
• Other Study ID Numbers: STCUBE-003CN-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No