Metastatic Colorectal Cancer (CRC), Recurrent Colorectal Cancer
Conditions
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.
Interventions
DRUGNelmastobart 800 mg+Trifluridine/Tipiracil+ Bevacizumab
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.
Sponsors
STCube, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects who participate in the study must meet all of the following inclusion criteria. 1. Adults ≥19 years old at the time of written informed consent 2. 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.) 3. Subjects with at least one evaluable lesion, or non-measurable but evaluable lesion according to RECIST v1.1 4. Subjects with ECOG performance status 0-1 5. 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 6. 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.) 7. A negative serum β-HCG test within 14 days prior to IP dosing for women of childbearing potential 8. Subjects 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. * Subjects 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. * 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. * 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. * 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. Subjects who consent to sampling tumor tissues or collecting tumor tissue samples obtained within 2 years prior to the screening visit 11. Subjects 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 \[Inclusion criteria for the phase 2 study\] Subjects who participate in the phase 2 study must meet all of the following criteria. 12. Subjects with Tumor Proportion Score (TPS) ≥50 based on immunohistochemistry (IHC) at the screening visit
Exclusion criteria
Individuals who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of DLT | up to 6 months | Status of DLT will be presented with frequency, percentage and its 95% confidence interval (CI). |
| RP2D(Recommended Phase 2 Dose) | up to 2 years | The recommended phase 2 dose (RP2D) of nelmastobart in combination with trifluridine/tipiracil and bevacizumab |
| MTD(Maximum Tolerated Dose) | up to 2 years | To find the maximum tolerated dose (MTD) |
| Progression Free Survival (PFS) rate | up to 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS(Progression free survival) | up to 2 years | Time from first dose until the date of objective disease progression or death |
| Phase 2 study; Duration of Response (DOR) | up to 2 years | Time from the date of first confirmed objective response (CR or PR) after investigational drug administration to the first documented disease progression (PD) or death from any cause, with documentation of disease progression status and cause of death |
| Phase 2 study; Overall Survival (OS) | up to 2 years | Time from the start of treatment to all cause death |
| Tmax(Time to Maximum Plasma Concentration) | up to 2 years | Time to reach Tmax of Nelmastobart to evaluate the PK parameters. |
| AEs(Adverse Events) | up to 2 years | 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. |
| Phase 2 study; Objective Response Rate (ORR) | up to 2 years | Investigator assessed ORR defined by RECIST 1.1 or iRECIST |
| Maximum plasma concentration (Cmax) | up to 6 months | Maximum plasma concentration of Nelmastobart to evaluate PK parameters |
| Phase 2 study; Disease Control Rate (DCR) | up to 2 years | Investigator assessed DCR at 16 weeks defined by RECIST 1.1 or iRECIST |
Countries
South Korea
Contacts
Primary ContactHyunju Yoo
Outcome results
None listed