A First-in-Human Escalation and Expansion Study of Patients with Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Solid Tumors; Gastric Cancer; Esophagogastric Juction Cancer; Colorectal Cancer
• Interventions: Drug: JR8603

• Registration Number: NCT06783569
• Lead Sponsor: JiaRay Group

Brief Summary

The goal of this clinical trial is to learn if the investigational drug (JR8603) is safe and effective in treating patients with solid tumors after their initial rounds of treatment with other drugs did not work.

Detailed Description

This is a 2-part, first-in-human, open-label study to determine the safety and tolerability and preliminary efficacy of JR8603 in patients with locally advanced or metastatic solid tumors who have progressed after or are intolerant to standard therapies. The study will include a Dose Escalation Part and a Dose Expansion Part. JR8603 will be administered as a short IV infusion on Days 1, 8, and 15 of continuous 28-day cycles. Safety and tolerability of JR8603 will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. All patients will be assessed for response using Response Criteria for Evaluation in Solid Tumors (RECIST) v1.1, with computed tomography (CT) or magnetic resonance imaging (MRI) occurring at screening within 28 days of first dose, then every 8 weeks (±7 days) after Cycle 1 Day 1 (C1D1) for the first year and every 12 weeks (±7 days) thereafter. Serial blood samples for determination of PK will be collected.

Study Timeline

• Study Start: 2024-12-31
• Status Verified: 2025-01
• Study First Submitted: 2025-01-07
• Study First Submitted QC: 2025-01-14
• Last Update Submitted: 2025-01-17
• Study First Posted: 2025-01-20
• Last Update Posted: 2025-01-21
• Primary Completion: 2026-05
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Escalation Cohort - Dose Level 4	JR8603	Dose Level 4: 21.0mg/m2. Dose escalation will follow 3+3 design rules with 3 patients enrolled in each dose level. If 3 patients complete the DLT period with no DLTs, that dose level of JR8603 will be deemed safe, and another 3 patients will be treated at the next higher dose level. If 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level of JR8603. If 2 or more of the 3 to 6 patients in any dose level experience a DLT, dosing will stop at that level.
Escalation Cohort - Dose Level -1	JR8603	Dose Level -1: 1.7mg/m2. A Dose Level -1 cohort will be introduced if a dose reduction to a lower level is required.
Expansion Cohort 1	JR8603	-
Expansion Cohort 2	JR8603	-
Escalation Cohort - Dose Level 1	JR8603	Dose Level 1: 3.3mg/m2. For Dose Levels 1 and 2, a single patient will be enrolled per dose level. If the patient in Dose Level 1 does not experience a Grade ≥2 adverse event (AE) that is not clearly attributed to an extraneous cause, such as the patient's underlying disease, other medical conditions, or concomitant medications or procedures during the dose-limiting toxicity (DLT) period, then Dose Level 2 will also be a single patient. If the patient in Dose Level 1 experiences a Grade ≥2 AE during the DLT period, then 2 additional patients will be added to Dose Level 1 and the remainder of the study will use 3+3 design rules.
Escalation Cohort - Dose Level 2	JR8603	Dose Level 2: 7.0mg/m2. If Dose Level 2 is qualified to be a single patient, and the patient does not experience a Grade ≥2 AE during the DLT period, then Dose Level 3 will proceed and the study, thereafter, will utilize 3+3 design rules. If the patient in Dose Level 2 experiences a Grade ≥2 AE during the DLT period, then 2 additional patients will be enrolled in Dose Level 2 and evaluated using 3+3 design rules.
Escalation Cohort - Dose Level 3	JR8603	Dose Level 3: 14.0mg/m2. From Dose Level 3 and thereafter, dose escalation will follow 3+3 design rules with 3 patients enrolled in each dose level. If 3 patients complete the DLT period with no DLTs, that dose level of JR8603 will be deemed safe, and another 3 patients will be treated at the next higher dose level. If 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level of JR8603. If 2 or more of the 3 to 6 patients in any dose level experience a DLT, dosing will stop at that level.
Escalation Cohort - Dose Level 5	JR8603	Dose Level 5: 28.0mg/m2. Dose escalation will follow 3+3 design rules with 3 patients enrolled in each dose level. If 3 patients complete the DLT period with no DLTs, that dose level of JR8603 will be deemed safe, and another 3 patients will be treated at the next higher dose level. If 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level of JR8603. If 2 or more of the 3 to 6 patients in any dose level experience a DLT, dosing will stop at that level.
Escalation Cohort - Dose Level 6	JR8603	Dose Level 6: 35.0mg/m2. Dose escalation will follow 3+3 design rules with 3 patients enrolled in each dose level. If 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level of JR8603. If 2 or more of the 3 to 6 patients in any dose level experience a DLT, dosing will stop at that level.

Primary Outcome Measures

Name	Time	Method
Adverse Events (Including Serious Adverse Events)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	The severity of all AEs will be graded according to the NCI CTCAE v5.0 criteria.
Dose-Limiting Toxicity (DLT)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Incidence of DLTs
Maximum tolerated dose (MTD)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Evaluated based on DLT-Evaluable patients in part 1 Dose Escalation
Dose Expansion - to assess preliminary evidence of efficacy for each cohort	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Measured by Overall Response Rate (ORR) as defined by RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Defined as the proportion of patients with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) per RECIST v1.1
Assess Plasma concentrations and relevant PK parameters for JR8603 and the active metabolite (mitomycin C)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Will be assessed based on blood samples collected from patients during the study.
Time to Response (TTR)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Defined as the time from the date of the first dose to the date at which criteria are first met for Complete Response (CR) or Partial Response (PR) per RECIST v1.1.
Duration of Response (DOR)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Defined as the time from the start of the first response (CR or PR) to the first occurrence of progressive disease per RECIST v1.1 or death due to any cause
Disease Control Rate (DCR)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Defined as the proportion of patients whose best overall response is a CR, PR, or stable disease (SD)
Progression-free survival (PFS)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Defined as the time from the first dose of JR8603 until the first documentation of disease progression or death due to any cause, whichever occurs first.
Overall survival (OS)	From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year	Defined as the time from the date of the first dose of study drug to the date of death due to any cause.

Trial Locations

Locations (1)

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin City, Heiljiang Providence, China