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

NCT06783569 | Recruiting Phase 1 FDA Drug

• 1 other identifier: JR8603-9101
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 2

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.

Conditions

Solid Tumors; Gastric Cancer; Esophagogastric Juction Cancer; Colorectal Cancer

Keywords

locally advanced solid tumors; metastatic solid tumors; intolerant to standard therapies; Mitomycin C

Outcome Measures

Primary Outcomes (4)

• Adverse Events (Including Serious Adverse Events)

  The severity of all AEs will be graded according to the NCI CTCAE v5.0 criteria.

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

• Dose-Limiting Toxicity (DLT)

  Incidence of DLTs

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

• Maximum tolerated dose (MTD)

  Evaluated based on DLT-Evaluable patients in part 1 Dose Escalation

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

• Dose Expansion - to assess preliminary evidence of efficacy for each cohort

  Measured by Overall Response Rate (ORR) as defined by RECIST v1.1.

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

• 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

• Time to Response (TTR)

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

• Duration of Response (DOR)

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

• Disease Control Rate (DCR)

  From study drug administration until 28 (±7) days after the last dose of study drug, up to approximately 1 year

Study Arms (9)

Escalation Cohort - Dose Level -1

EXPERIMENTAL

Dose Level -1: 1.7mg/m2. A Dose Level -1 cohort will be introduced if a dose reduction to a lower level is required.

Drug: JR8603

Escalation Cohort - Dose Level 1

EXPERIMENTAL

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.

Drug: JR8603

Escalation Cohort - Dose Level 2

EXPERIMENTAL

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.

Drug: JR8603

Escalation Cohort - Dose Level 3

EXPERIMENTAL

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.

Drug: JR8603

Escalation Cohort - Dose Level 4

EXPERIMENTAL

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.

Drug: JR8603

Escalation Cohort - Dose Level 5

EXPERIMENTAL

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.

Drug: JR8603

Escalation Cohort - Dose Level 6

EXPERIMENTAL

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.

Drug: JR8603

Expansion Cohort 1

EXPERIMENTAL

Drug: JR8603

Expansion Cohort 2

EXPERIMENTAL

Drug: JR8603

Interventions

JR8603 DRUG

IV infusion on Days 1, 8, and 15 of continuous 28-day cycles

Escalation Cohort - Dose Level -1; Escalation Cohort - Dose Level 1; Escalation Cohort - Dose Level 2; Escalation Cohort - Dose Level 3; Escalation Cohort - Dose Level 4; Escalation Cohort - Dose Level 5; Escalation Cohort - Dose Level 6; Expansion Cohort 1; Expansion Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age.
• Histologically confirmed, locally advanced, or metastatic solid tumor which has progressed on, or patients intolerant to, all standard therapy, or no standard therapy available, or it is documented that the therapy is refused by the patient.
• Measurable disease per RECIST v1.1.
• Life expectancy ≥3 months.
• Adequate organ and bone marrow function defined by:
• Absolute neutrophil count (ANC) ≥1.5 × 109/L (≥1500/mm3)
• Platelet count ≥100 × 109/L (≥100,000/mm3) (no platelet transfusion within 14 days prior to enrollment)
• Total bilirubin ≤1.5 × upper limit of normal (ULN), unless known Gilbert syndrome (≤3 × ULN) has been diagnosed
• AST and ALT ≤2.5 × ULN or ≤5 × ULN for patients with known liver metastases
• Estimated creatinine clearance by the Cockcroft-Gault or estimated glomerular filtration rate (eGFR) of ≥60 mL/min
• International Normalized Ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5 × ULN. If a patient is receiving anticoagulant therapy, PT and aPTT must be within therapeutic range of intended use of anticoagulants
• Patients with treated, stable central nervous system (CNS) metastases (including leptomeningeal carcinomatosis) are allowed if there is no evidence of progression for at least 4 weeks after CNS-directed treatment as ascertained by clinical examination and brain imaging.
• Resolution of any clinically significant toxic effects of prior therapy to Grade ≤1 according to the NCI CTCAE v5.0 (exception of alopecia and Grade 2 peripheral neuropathy).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Willingness of men and women of reproductive potential to observe conventional and effective birth control methods with failure rates of \<1% for the duration of treatment and for at least 6 months for women and at least 3 months for men following the last dose of study treatment (this must include a barrier method such as condom or diaphragm with spermicidal gel). Women of reproductive potential are defined as following menarche and who are not postmenopausal (and 2 years of nontherapy-induced amenorrhea or surgically sterile). For male patients with a nonpregnant female partner of childbearing potential and a woman of childbearing potential, 1 of the following highly effective birth control methods with a failure rate of less than 1% per year when used consistently and correctly are recommended:

You may not qualify if:

• Any condition that in the opinion of the Investigator would place the patient at an unacceptable risk or cause the patient to be unlikely to fully participate or comply with study procedures.
• Received systemic anticancer chemotherapy, targeted agents, antibody therapy for cancer, immunotherapy for cancer, hormonal therapy, or an investigational agent within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study drug treatment.
• Major surgery within 3 weeks prior to start of study drug treatment.
• Radiation therapy within 4 weeks prior to start of study drug treatment (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study drug treatment). Patients must have recovered from all acute radiotherapy-related toxicities.
• Severe or unstable cardiac conditions including, but not limited to, congestive heart failure (New York Heart Association Class III or IV), ischemic heart disease, uncontrolled hypertension, uncontrolled cardiac arrhythmia requiring medication (Grade ≥2, according to NCI CTCAE v5.0), myocardial infarction within 6 months prior to starting study drug treatment, congenital long QT syndrome or QT interval corrected for heart rate using Fridericia's formula (QTcF) \>470 msec at screening, and any other significant or unstable concurrent cardiac illness.
• Severe or unstable medical condition including uncontrolled diabetes or unstable psychiatric condition.
• Has a history of another active malignancy (a second cancer) within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, present a low risk of recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• Active infection requiring systemic therapy (including asymptomatic infections with positive virus titers and the Investigator's judgment that worsening of the condition is likely with study drug or the condition will impair or prohibit a patient's participation in the study).
• Known human immunodeficiency virus, hepatitis B virus (HBV) (i.e., hepatitis B surface antigen positive), or hepatitis C virus (HCV) (i.e., detectable HCV ribonucleic acid \[RNA\]). Note: Patients with a prior history of treated HBV infection who are antigen negative, patients with a prior history of treated HCV infection who are HCV RNA undetectable, or patients with HIV who are on stable anti-retroviral therapy and have an undetectable viral load may be enrolled.
• Pregnant (or intending to become pregnant) or breastfeeding.

Sponsors & Collaborators

• JiaRay Group: lead

Study Sites (2)

Harbin Medical University Cancer Hospital

Harbin, Heiljiang Province, 150040, China

RECRUITING

Liaoning Cancer Hospital

Shenyang, Liaoning, 110042, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Sam Chu

CONTACT

760-351-6988; samchu@jiaraygroup.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1: Dose Escalation- will consist of accelerated titration followed by traditional 3+3 design. The accelerated titration portion may consist of up to 3 patients in the first 2 dose levels and the 3+3 ascending dose escalation portion will consist of 3 to 6 patients per dose level. Part 2: Dose Expansion- each cohort will be enrolled independently following a Simon's 2-Stage optimal design. In the first stage, 10 evaluable patients will be enrolled. If there is only 1 or no response in these 10 patients, the cohort will be stopped. Otherwise, 19 additional evaluable patients will be accrued to that cohort for a total of 29 evaluable patients.

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: January 20, 2025
• Study Start: December 31, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 9, 2025

Record last verified: 2025-09

Locations

CN (2)