Phase I Study to Evaluate the Safety ,Tolerability, and Pharmacokinetics of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 102
- Locations
- 1
- Primary Endpoint
- Dose Limited Toxicity(DLT)
Study Overview
Brief Summary
The study is being conducted to evaluate the safety and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation.To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
- •Male or female ≥ 18 years old.
- •Histologically confirmed diagnosis of advanced solid tumor harbouring with KRAS G12D mutation
- •ECOG performance status of 0-
- •With a life expectancy of ≥3 months.
- •Have at least one measurable lesion.
- •Adequate laboratory parameters during the screening period
Exclusion Criteria
- •Previously received KRAS G12D inhibitors
- •Priot radiotherapy within 28 days for non-thoracic radiation
- •Prior anti-tumor chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or mitomycin) within 4 weeks before the study drug administration
- •Any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or inclusion/exclusion criteria level (The investigators determined that safe and controllable toxicity was excluded, such as alopecia and ≤ grade 2 peripheral neuropathy ).
- •Central nervous system (CNS) metastases
- •Major surgical therapy within 28 days prior to the date of signature of informed consent form, or expected major surgery during the study.
- •Known history of hypersensitivity to any components of HRS-
- •Other factors that may affect the study results or lead to forced termination of the study early as judged by investigators.
Arms & Interventions
HRS-4642
In Dose Escalation:
HRS-4642 will be injected QW. Six dose levels are preset.
In Dose Expansion:
1 to 2 dose cohorts will be selected for dose expansion stage.
In Indication Expansion:
Enrollment into the dose expansion cohorts may be from any eligible solid tumor type.
Intervention: HRS-4642 (Drug)
Outcomes
Primary Outcomes
Dose Limited Toxicity(DLT)
Time Frame: from day 1 to Day 21
A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness
Maximum tolerated dose (MTD)
Time Frame: From Day 1 to Day 21
Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of HRS-4642 treatment.
Safety endpoints: adverse events(AEs), serious adverse events（SAEs）.
Time Frame: 24 months
Assess safety and tolerability of HRS-4642 by way of adverse events (CTCAE v5.0).
RP2D
Time Frame: 24 months
RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.
Secondary Outcomes
- AUC.(24 months.)
- t1/2.(24 months.)
- Number of subjects with changes on ECG.(24months.)
- Number of subjects with clinically significant changes in ECOG, vital signs and physical examination.(24months.)
- Efficacy endpoints: Progression free survival (DoR).(24months.)
- Vz/F.(24 months.)
- Efficacy endpoints: Disease control rate (DCR).(24months.)
- Efficacy endpoints: overall survival (OS).(24minths)
- Cmax.(24 months.)
- Number of Participants With Abnormal Laboratory Values(24months.)
- Efficacy endpoints: Overall response rate (ORR).(24months.)
- Efficacy endpoints: Duration of response (DoR).(24 months.)
- Tmax.(24 months)
- CL/F.(24 months.)