A Clinical Study of IMP4297 Capsule (JS109) Combined With Irinotecan in the Treatment of Advanced Malignant Solid Tumors

NCT05824455 | Terminated Phase 1 DMC

• 1 other identifier: JS109-003-Ib/II
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The Phase Ib study was designed to evaluate the safety of JS109 in combination with irinotecan in the treatment of advanced solid tumors and to determine the Phase II recommended dose (RP2D). The Phase II study was designed to evaluate the efficacy and safety of the combination regimen in patients with extensive small-cell lung cancer (SCLC) that failed first-line platinum-containing regimen.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Incidence of DLT

  The Incidence of dose-limiting toxicity（DLT）

  Up to approximately 16 months from first patient in.

• Incidence and severity of AE

  The incidence and severity of adverse events (AE)

  Up to approximately 16 months from first patient in.

• Incidence and severity of SAE

  The incidence and severity of serious adverse events (SAE)

  Up to approximately 16 months from first patient in.

• Abnormal changes in laboratory and other tests of clinical significance

  The incidence and severity of abnormal changes in laboratory and other tests of clinical significance

  Up to approximately 16 months from first patient in.

Secondary Outcomes (21)

• MTD

  Up to approximately 16 months from first patient in.

• RP2D

  Up to approximately 16 months from first patient in.

• Tmax

  Up to approximately 16 months from first patient in.

• Cmax

  Up to approximately 16 months from first patient in.

• AUC0-T

  Up to approximately 16 months from first patient in.

Study Arms (1)

JS109 combination with irinotecan

EXPERIMENTAL

Combination Product: JS109 combine with irinotecan

Interventions

JS109 combine with irinotecan COMBINATION_PRODUCT

JS109 PO,QD, q3w combine with irinotecan(65mg/m2,IV,D1,8,Q3w)

JS109 combination with irinotecan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects voluntarily participated in the study with full informed consent and signed written informed consent form;
• Aged ≥18 years and ≤75 years when the subject signed the informed consent;
• Histologically confirmed advanced malignant solid tumor(phase Ib: Subjects with advanced malignant solid tumors who have failed standard therapy, do not currently have or refuse standard therapy, or are intolerant to standard therapy, and who have received no more than 3 lines of systemic therapy for advanced disease;phase II:Subjects with extensive stage SCLC who developed disease progression after receiving only the first-line standard platinum-containing regimen; Or subjects with localized SCLC who have progressed or relapsed after receiving prior chemoradiotherapy (platinum-containing chemotherapy), and the treatment free interval from the end of chemotherapy, radiotherapy, or chemoradiotherapy to the diagnosis of extensive stage SCLC is no more than 6 months);
• There should be at least one measurable lesion according to RECIST V1.1 evaluation criteria(Phase II only);
• The expected survival is ≥3 months;
• The physical status score is 0 or 1 on the Eastern Oncology Collaboration (ECOG) scale;
• Good organ function;
• Within 7 days prior to the first dose, women of reproductive age must be confirmed as having a negative serum pregnancy test and consent to use effective contraception during the duration of study drug use and for 90 days after the last dose. Male patients with a female partner of reproductive age agreed to use effective contraception during the study drug use period and for 90 days after the last dose.

You may not qualify if:

• Histologically confirmed combined SCLC or transformed SCLC ;
• Known allergy to study drug or excipients;
• Prior treatment with drugs or other therapies that target PARP;
• Had been treated with irinotecan in the past;
• Inability to swallow oral formulations and gastrointestinal dysfunction may interfere with study drug absorption;
• Subjects with malignancies other than target cancer (other than cured cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ of the breast) within 5 years prior to the first dose ;
• Pregnant or lactating female subjects;
• Myelodysplastic syndrome (MDS)/acute myelocytic cell (AML) leukemia subjects;
• Known history of allogeneic organ transplantation or allohematopoietic stem cell transplantation;
• Active central nervous system metastasis. Treated subjects with brain metastases were enrolled if they met the following criteria: corticosteroid therapy should be discontinued at least 7 days before the first dose; No disease progression was observed on imaging examinations from the end of brain orientation therapy to the time of randomization, when compared with pre-treatment imaging (at least 4 weeks apart);
• Known to have Gillbert syndrome;
• Clinically significant gastrointestinal disorders such as chronic inflammatory bowel disease and/or intestinal obstruction or diarrhea \> grade 1.
• Poorly controlled pleural effusion, peritoneal effusion or pericardial effusion (Hydrothorax and Ascites drainage frequency ≥1 time/month); Subjects who need to be stabilized for at least 1 week prior to the first dose after drainage (stable is defined as no definite increase in pleural fluid without any intervention) can be enrolled;
• Poorly controlled tumor-related pain;
• Myocardial infarction, severe/unstable angina, NYHA grade 2 or higher cardiac insufficiency, clinically significant supracentricular or ventricular arrhythmias, and symptomatic congestive heart failure, hypertensive crisis, or hypertensive encephalopathy during the 6 months preceding of the first dose; Known hypertension, coronary artery disease, congestive heart failure, congestive heart failure that does not meet the above criteria or patients with left ventricular ejection fraction \<50% must be treated with an optimal stabilization regimen as determined by the treating physician;

Sponsors & Collaborators

• Shanghai Jun Pai Ying Shi Therapeutics Co., Ltd.: lead
• Sponsor GmbH: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510062, China

Location

MeSH Terms

Interventions

Irinotecan

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Li Zhang, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Sequential

Study Record Dates

• First Submitted: April 9, 2023
• First Posted: April 21, 2023
• Study Start: March 23, 2023
• Primary Completion: September 28, 2023
• Study Completion: September 28, 2023
• Last Updated: September 5, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)