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Phase I Study of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation

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ClinicalTrials.gov Identifier: NCT05533463
Recruitment Status : Recruiting
First Posted : September 9, 2022
Last Update Posted : November 7, 2023
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

Study Description
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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

Condition or disease Intervention/treatment Phase
Advanced KRAS G12D Mutant Solid Tumors Drug: HRS-4642 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm study of HRS-4642
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study to Evaluate the Safety ,Tolerability, and Pharmacokinetics of HRS-4642 in Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation
Actual Study Start Date : September 15, 2022
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : December 30, 2024
Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.

 Drug: HRS-4642
HRS-4642 will be administrated per dose level in which the patients are assigned.


Outcome Measures
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Primary Outcome Measures :
  1. 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).

  2. 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

  3. 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.

  4. 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 Outcome Measures :
  1. Number of Participants With Abnormal Laboratory Values [ Time Frame: 24months. ]
  2. Number of subjects with clinically significant changes in ECOG, vital signs and physical examination. [ Time Frame: 24months. ]
  3. Number of subjects with changes on ECG. [ Time Frame: 24months. ]
  4. Efficacy endpoints: Overall response rate (ORR). [ Time Frame: 24months. ]
    Evaluated by RECIST v1.1.

  5. Efficacy endpoints: Duration of response (DoR). [ Time Frame: 24 months. ]
    Evaluated by RECIST v1.1

  6. Efficacy endpoints: Disease control rate (DCR). [ Time Frame: 24months. ]
    Evaluated by RECIST v1.1.

  7. Efficacy endpoints: Progression free survival (DoR). [ Time Frame: 24months. ]
    Evaluated by RECIST v1.1.

  8. Efficacy endpoints: overall survival (OS). [ Time Frame: 24minths ]
    Evaluated by RECIST v1.1

  9. Cmax. [ Time Frame: 24 months. ]
    Maximal plasma concentration.

  10. Tmax. [ Time Frame: 24 months ]
    Time to Cmax.

  11. AUC. [ Time Frame: 24 months. ]
    Area under the plasma concentration-time curve.

  12. t1/2. [ Time Frame: 24 months. ]
    Terminal-phase elimination half-life.

  13. Vz/F. [ Time Frame: 24 months. ]
    Apparent volume of distribution during terminal phase after non-intravenous administration.

  14. CL/F. [ Time Frame: 24 months. ]
    Apparent total clearance of the drug from plasma after oral administration.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  3. Histologically confirmed diagnosis of advanced solid tumor harbouring with KRAS G12D mutation
  4. ECOG performance status of 0-1.
  5. With a life expectancy of ≥3 months.
  6. Have at least one measurable lesion.
  7. Adequate laboratory parameters during the screening period

Exclusion Criteria:

  1. Previously received KRAS G12D inhibitors
  2. Priot radiotherapy within 28 days for non-thoracic radiation
  3. Prior anti-tumor chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or mitomycin) within 4 weeks before the study drug administration
  4. 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 ).
  5. Central nervous system (CNS) metastases
  6. Major surgical therapy within 28 days prior to the date of signature of informed consent form, or expected major surgery during the study.
  7. Known history of hypersensitivity to any components of HRS-4642.
  8. Other factors that may affect the study results or lead to forced termination of the study early as judged by investigators.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05533463


Contacts
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Contact: Wei Shi +021-61053363 Wei.shi@hengrui.com

Locations
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China, Shanghai
Shanghai Pulmonary Hospital Recruiting
ShangHai, Shanghai, China, 200433
Principal Investigator: Caicun Zhou         
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
More Information
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Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT05533463    
Other Study ID Numbers: HRS-4642-I-101
First Posted: September 9, 2022    Key Record Dates
Last Update Posted: November 7, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms