Clinical trial NCT06385678: A Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
Official title: A Phase IB/II Clinical Study on the Safety, Tolerability and Efficacy of HRS-4642 in Combination With Anti-tumor Medication in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: Advanced KRAS G12D Mutant Solid Tumors
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-04-26
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is being conducted to evaluate the safety, tolerability, and efficacy of HRS-4642 in combination with antitumor medicine in patients with advanced solid tumors harboring KRAS G12D mutation.


Eligibility criteria: Inclusion Criteria:

1. Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
2. Male or female ≥ 18 years old and ≤75 years old.
3. ECOG performance status of 0-1.
4. With a life expectancy of ≥12 weeks.
5. With unresectable locally advanced or metastatic solid tumors harbouring with KRAS G12D mutation confirmed by central laboratory testing.
6. Need to provided tumor tissue samples for genetic testing.
7. Have at least one measurable lesion according to RECIST1.1, and the dose-escalation phase allows no measurable lesion.
8. Adequate laboratory parameters during the screening period.

Exclusion Criteria:

1. Accompanied by untreated or active central nervous system (CNS) metastases. Subjects with a history or current history of meningeal metastasis.
2. Systemic antitumor therapy was received 4 weeks before the start of the study.
3. Palliative radiotherapy was completed within 14 days before the first dose.
4. Toxicity and/or complications from previous interventions did not return to NCI-CTCAE level ≤1 or exclusion criteria.
5. Subjects with known or suspected interstitial pneumonia.
6. Moderate or severe ascites with clinical symptoms; Uncontrolled or moderate or higher pleural effusion or pericardial effusion.
7. Have poorly controlled or severe cardiovascular disease.
8. Subjects with active hepatitis B or active hepatitis C.
9. A history of immunodeficiency, including a positive HIV test, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.
10. The presence of uncontrolled mental illness and other conditions known to affect the completion of the study process, such as alcohol, drug or substance abuse, and criminal detention.
11. Any other factors that may increase the risk of participating in the study, interfere with the study results, or make participation in the study inappropriate as judged by investigators.

Primary outcomes:
measure: Phase IB: Safety endpoints: adverse events (AEs).
timeFrame: 24 months
measure: Phase IB： Maximum tolerated dose (MTD)
timeFrame: From Day 1 to Day 21
measure: Phase IB：Recommended phase 2 dose (RP2D)
timeFrame: 24 months
measure: Phase II: Overall response rate (ORR).
timeFrame: 24 months.
Secondary outcomes:
measure: Efficacy endpoints: Overall response rate (ORR).
timeFrame: 24 months
measure: Efficacy endpoints: Duration of response (DoR).
timeFrame: 24 months
measure: Efficacy endpoints: Disease control rate (DCR).
timeFrame: 24 months
measure: Efficacy endpoints: Progression free survival (PFS).
timeFrame: 24 months
measure: Efficacy endpoints: overall survival (OS).
timeFrame: 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
References: