A Phase Ib/III Study of Suvemcitug Plus FTD/TPI in Participants With Refractory Metastatic Colorectal Cancer

Official title

A Phase Ib/III Study of Suvemcitug Plus Trifluridine/Tipiracil Tablets (FTD/TPI) Versus Placebo Plus Trifluridine/Tipiracil Tablets in Participants With Refractory Metastatic Colorectal Cancer

Overview

The primary goal of Phase Ib Study is to evaluate the safety of Suvemcitug in combination with trifluridine/tipiracil tablets in colorectal cancer participants. The primary goal of Phase III Study is to evaluate the efficacy of Suvemcitug in combination with trifluridine/tipiracil tablets in colorectal cancer participants. Researchers will compare Suvemcitug + trifluridine/tipiracil tablets with placebo (a look-alike substance that contains no drug)+ trifluridine/tipiracil tablets to see if Suvemcitug + trifluridine/tipiracil tablets works better in treating refractory metastatic colorectal cancer.

Detailed description

The study will enroll approximately 464 participants (30 for Phase Ib and 434 for Phase III stage) with refractory metastatic colorectal cancer who have previously received fluorouracil, oxaliplatin, and irinotecan-based chemotherapy, and who have either previously received or are unsuitable for anti-vascular endothelial growth factor (VEGF) therapy or anti-epidermal growth factor receptor (EGFR) therapy (RAS wild-type).

For Phase Ib Study, all 30 participants will be receiving the treatment with Suvemcitug in combination with trifluridine/tipiracil tablets. For Phase III Study, approximately 434 participants will be randomly assigned in a 1:1 ratio to two groups. One group will receive treatment with Suvemcitug + trifluridine/tipiracil tablets. The other group will receive the treatment with placebo + trifluridine/tipiracil tablets.

All participants will receive study treatment until they meet the criteria for treatment discontinuation. During study treatment period, investigators will evaluate the efficacy, safety and participants' quality of life. After treatment discontinuation, investigators will continue to follow up for subsequent treatment and survival information until the criteria for study discontinuation are met.

By the end of study, for participants who are still receiving study treatment, if their efficacy evaluation result is stable or response and they are tolerant to the treatment, then after obtaining approval from health regulatory authorities and ethics committees, they can continue study treatment by joining another extension study or in other ways as discussed by the sponsor.

Interventions

• Drug Suvemcitug injection, trifluridine/tipiracil tablets
  Suvemcitug injection at 1.5mg/kg, Trifluridine/tipiracil tablets at 35 mg/m²
• Drug Suvemcitug placebo injection, trifluridine/tipiracil tablets
  Suvemcitug placebo injection, Trifluridine/tipiracil tablets at 35 mg/m².

Primary outcome measures

• Phase Ib: dose limiting toxicity (DLT) [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Phase Ib: Adverse Events [Time frame: From signing informed consent form until 28 days after the last dose of study treatment, up to about 18 months]
• Phase Ib: Tolerance [Time frame: From signing informed consent until 28 days after the last dose of study treatment, for up to 18 months]
• Phase III: overall survival (OS) [Time frame: For about 18 months from the randomization of the last participant]

Secondary outcome measures (12)

• Suvemcitug Serum concentration change over time of all participants [Time frame: For about 6 cycles, each cycle is 28 days.]
• Peak Suvemcitug serum concentration (Cmax) of all participants [Time frame: For about 6 cycles, each cycle is 28 days]
• The time taken to reach peak Suvemcitug concentration after administration (Tmax) [Time frame: For about 6 cycles, each cycle is 28 days]
• The time required for Suvemcitug concentration in the serum to decrease by half (t1/2) [Time frame: For about 6 cycles, each cycle is 28 days]
• Serum anti-drug antibody (ADA) incidence of Suvemcitug [Time frame: For about 6 cycles, each cycle is 28 days]
• Serum anti-drug antibody (ADA) duration of Suvemcitug [Time frame: For about 6 cycles, each cycle is 28 days]
• Serum anti-drug antibody (ADA) titer of Suvemcitug [Time frame: For about 6 cycles, each cycle is 28 days]
• Objective Response Rate (ORR) of all participants [Time frame: From the date when the first dose of Suvemcitug is administered until radiological progression, initiation of new anti-cancer therapy, death or withdrawal from study, whichever came first, assessed up to 18 months.]
• Duration of response (DoR) of all participants [Time frame: From the date when the first dose of Suvemcitug is administered until radiological progression, initiation of new anti-cancer therapy, death or withdrawal from study, whichever came first, assessed up to 18 months]
• Disease control rate (DCR) of all participants [Time frame: From the date when the first dose of Suvemcitug is administered until radiological progression, initiation of new anti-cancer therapy, death or withdrawal from study, whichever came first, assessed up to 18 months.]
• Progression free survival (PFS) of all participants [Time frame: From the date when the first dose of Suvemcitug is administered until radiological progression, initiation of new anti-cancer therapy, death or withdrawal from study, whichever came first, assessed up to 18 months.]
• Phase Ib: overall survival (OS) [Time frame: For about 18 months from the randomization of the last participant]

Eligibility criteria

Inclusion criteria

• 1\. Confirmed by histological and/or cytological examination as unresectable metastatic colon or rectal adenocarcinoma;
• 2\. At least one measurable tumor lesion (RECIST v1.1);
• 3\. Previously received fluorouracil, oxaliplatin, and irinotecan based chemotherapy; had previously undergone or was unsuitable for anti-VEGF therapy. (For participants with RAS wild-type, had previously undergone or was unsuitable for anti-EGFR therapy.);
• 4\. Refractory metastatic colorectal cancer having progressed on or are intolerant to the last systemic treatment;
• 5\. Good organ and bone marrow function (no administration of hematopoietic growth factors, blood transfusion, or platelets within 14 days before screening hematology test);
• 6\. RAS mutation status confirmed by testing tumor tissue and /or blood sample.

Exclusion criteria

• 1\. Having a second active primary malignancy within the past 5 years;
• 2\. Symptomatic central nervous system (CNS) metastases or CNS metastases requiring local CNS-directed therapy (e.g., radiotherapy or surgery) or corticosteroid treatment within 2 weeks prior to the first administration of the study treatment;
• 3\. Any active infection requiring systemic treatment within 2 weeks prior to the initiation of the study treatment;
• 4\. Pleural effusion, pericardial effusion, or ascites that is uncontrolled or has required drainage or medical intervention within 4 weeks prior to the first administration of the study treatment;
• 5\. Received systemic immuno suppressive therapy within 4 weeks prior to randomization (excluding prophylactic use or chronic low-dose steroids \[≤20 mg/day prednisone equivalent dose\]);
• 6\. Currently taking or has recently taken (within 10 days prior to the first dose) aspirin (>325 mg/day);
• 7\. Active or chronic hepatitis B (HBsAg or HBcAb positive and HBV DNA≥2000 IU/mL or ≥10000 copies/mL) or hepatitis C infection (HCV antibody positive and HCV RNA≥ULN);
• 8\. Clinically significant cardiovascular disease within 6 months prior to the first administration of the study treatment;symptomatic coronary artery disease requiring medication; arrhythmia requiring medication (excluding asymptomatic atrial fibrillation with controlled ventricular rate); QTcF interval >470 ms at rest state; or uncontrolled hypertension or pulmonary hypertension;
• 9\. Known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.); clinically significant bleeding events, arterial or deep venous thrombotic events, or superficial venous thrombosis and intermuscular venous thrombosis requiring intervention within 6 months prior to enrollment;
• 10\. Participants with proteinuria (urine protein >2+ found during screening examinations; or urine protein 2+ with 24-hour urine protein quantification ≥1g/24h);
• 11\. Participants with a history of intestinal obstruction (including incomplete intestinal obstruction) within 1 month prior to enrollment; participants with a history of abdominal fistula, gastrointestinal perforation, or abdominal abscess.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 6 centers

• Fujian Cancer Hospital — Fuzhou
• Harbin Medical University University Cancer Hospital — Harbin
• The First Affiliated Hospital of Nanjing Medical University — Nanjing
• Cancer Hospital of Shandong First Medical University — Jinan
• Tianjin Medical University Cancer Institute and Hospital — Tianjin
• The Second Affiliated Hospital Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07361003 · SIM0063-302 · CTR20254831

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20254831 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗