Colonrectal Cancer (CRC)
Conditions
Brief summary
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.
Interventions
DRUGNelmastobart in combination with TAS-102 and Bevacizumab
1. 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. 2. Drug name: Qufluorodeoxyuridine/tipiracil. Specifications: 15mg, 20mg. Formulation: film-coated tablet. Batch number: XXX. Produced and supplied by Taiho Pharmaceutical Co., Ltd. 3. 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)
Sponsors
STCube, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of DLT | up to 6 months | 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." |
| Permanent discontinuation of IP due to adverse drug reactions (ADRs) | up to 6 months | The incidence and rate of permanent discontinuation of IP due to adverse drug reactions (ADRs) |
| AEs(Adverse Events) | up to 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) | up to 6 months | Maximum plasma concentration of Nelmastobart to evaluate PK parameters for the first and the subsequent cycles. |
| Objective response rate (ORR) | up to 6 months | To evaluated by the Independent Review Committee (IRC) in accordance with the RECIST1.1 criteria. |
| Immunogenicity indicators: | up to 6 months | Incidence of antibody formation against drugs (ADA) |
| Tmax(Time to Maximum Plasma Concentration) | up to 6 months | Time to reach Tmax of Nelmastobart to evaluate the PK parameters for the first and the subsequent cycles. |
| ORR assessed by researchers | up to 6 months | ORR assessed primarily by researchers based on the RECIST1.1 criteria. |
Contacts
CONTACTZhang Jian, M.D
Outcome results
None listed