Advanced KRAS G12D Mutant Solid Tumors
Conditions
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.
Interventions
DRUGHRS-4642
administrated per dose level in which the patients are assigned
DRUGAdebrelimab
administrated per dose level in which the patients are assigned
DRUGSHR-9839
administrated per dose level in which the patients are assigned
DRUGPemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection
administered as prescribed by the investigator.
administrated per dose level in which the patients are assigned
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase IB: Safety endpoints: adverse events (AEs). | 24 months | Assess safety and tolerability by way of adverse events (CTCAE v5.0). |
| Phase IB： Maximum tolerated dose (MTD) | From Day 1 to Day 21 | Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of treatment. |
| Phase IB：Recommended phase 2 dose (RP2D) | 24 months | RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages. |
| Phase II: Overall response rate (ORR). | 24 months. | Evaluated by RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy endpoints: Overall response rate (ORR). | 24 months | Evaluated by RECIST v1.1. |
| Efficacy endpoints: overall survival (OS). | 24 months | Evaluated by RECIST v1.1. |
| Efficacy endpoints: Duration of response (DoR). | 24 months | Evaluated by RECIST v1.1. |
| Efficacy endpoints: Disease control rate (DCR). | 24 months | Evaluated by RECIST v1.1. |
| Efficacy endpoints: Progression free survival (PFS). | 24 months | Evaluated by RECIST v1.1. |
Countries
China
Outcome results
None listed