An Open-Label, Multi-center Phase 1/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Activity of 3HP-2827 in Patients With Unresectable or Metastatic Solid Tumors With FGFR2 Alterations
Overview
- Phase
- Phase 1
- Intervention
- 3HP-2827
- Conditions
- Solid Tumors With FGFR2 Alterations, Adult
- Sponsor
- 3H (Suzhou) Pharmaceuticals Co., Ltd.
- Enrollment
- 130
- Locations
- 2
- Primary Endpoint
- Dose Escalation Stage- incidence of adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The study is being conducted to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of 3HP-2827 in the treatment of unresectable or metastatic solid tumors with FGFR2 alterations.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The patient is willing and able to provide written informed consent and has the ability to comply with the study protocol
- •Men or women, age ≥ 18 years at the time of signing informed consent.
- •Histologically or cytologically confirmed surgically unresectable, locally advanced, metastatic solid tumor.
- •ECOG score is 0 or
- •An expected survival of ≥ 12 weeks.
- •Evaluable or measurable disease per RECIST v1.
- •Adequate organ function, as measured by laboratory values.
Exclusion Criteria
- •Active brain metastases.
- •Have other malignancies within the past 3 years.
- •The toxicity from previous anti-tumor treatment has not recovered to ≤ grade
- •Clinically significant corneal or retinal disease/keratopathy.
- •Clinically significant cardiovascular disorders.
- •Failure to swallow, chronic diarrhea, or presence of other factors affecting drug absorption.
- •Known to be allergic to any study drug or any of its excipients.
- •Assessed by the investigator to be unsuitable for participation in this study.
Arms & Interventions
Stage I - dose escalation
Dose escalation of 3HP-2827 in patients with advanced solid tumors.
Intervention: 3HP-2827
Stage II - expansion
Expansion evaluating the recommended dose and schedule of 3HP-2827 identified from Stage I.
Intervention: 3HP-2827
Outcomes
Primary Outcomes
Dose Escalation Stage- incidence of adverse events (AEs)
Time Frame: From baseline up until 28 days after the final dose
Dose Escalation Stage- incidence of dose-limiting toxicities (DLTs)
Time Frame: Days 1-28 of Cycle 1 (a cycle is 28 days)
Dose Escalation Stage -determine the maximum tolerated dose (MTD) and/or the recommended dose (RD) for expansion stage or recommended Phase II dose (RP2D) of 3HP-2827
Time Frame: Initiation of study drug until study discontinuation, (up to approximately 24 months)
Expansion stage -Objective response rate（ORR）
Time Frame: Initiation of study drug until disease progression (up to approximately 36 months)
ORR refers to the percentage of patients with best overall response of confirmed CR or PR from the start of study treatment to patient withdrawal due to PD.
Dose Escalation Stage -Percentage of Participants With Changes From Baseline in Targeted ECG Parameters
Time Frame: From baseline up until 28 days after the final dose
Dose Escalation Stage -Percentage of Participants With Changes From Baseline in Targeted Clinical Laboratory Test Results
Time Frame: From baseline up until 28 days after the final dose
Dose Escalation Stage -Percentage of Participants With Changes From Baseline in Targeted Vital Signs
Time Frame: From baseline up until 28 days after the final dose
Secondary Outcomes
- Apparent volume of distribution (Vz/F) of 3HP-2827 and/or its major metabolites as monotherapy.(Initiation of study drug until study discontinuation, (up to approximately 24 months)))
- Disease control rate (DCR) as assessed by RECIST v1.1(Up to 45 months)
- Progression-free survival (PFS) as assessed by RECIST v1.1(Up to 45 months)
- Expansion Stage- incidence of adverse events (AEs)(From baseline up until 28 days after the final dose)
- Expansion Stage -Percentage of Participants With Changes From Baseline in Targeted Vital Signs(From baseline up until 28 days after the final dose)
- Overall survival (OS)(Up to 48 months)
- Maximum concentration (Cmax) during the dosing interval of 3HP-2827 and/or its major metabolites as monotherapy.(Initiation of study drug until study discontinuation, (up to approximately 24 months)))
- Duration of Response (DOR) as assessed by RECIST v1.1(Up to 45 months)
- Expansion Stage -Percentage of Participants With Changes From Baseline in Targeted ECG Parameters(From baseline up until 28 days after the final dose)
- Dose escalation stage - Objective Response Rate (ORR)(Up to 45 months)
- Expansion Stage -Percentage of Participants With Changes From Baseline in Targeted Clinical Laboratory Test Results(From baseline up until 28 days after the final dose)
- Expansion Stage -Changes in patient-reported outcomes as assessed by the European Organization for Research and Treatment of Cancer Core QoL Questionnaire (EORTC QLQ-C30) in patients with advanced solid tumors(From baseline up until 28 days after the final dose)
- Time to maximum concentration (Tmax) of 3HP-2827 and/or its major metabolites as monotherapy.(Initiation of study drug until study discontinuation, (up to approximately 24 months)))
- Apparent clearance (CL/F) of 3HP-2827 and/or its major metabolites as monotherapy.(Initiation of study drug until study discontinuation, (up to approximately 24 months)))
- Area under the concentration-time curve (AUC) of 3HP-2827 and/or its major metabolites as monotherapy.(Initiation of study drug until study discontinuation, (up to approximately 24 months)))
- Terminal half life (t1/2) of 3HP-2827 and/or its major metabolites as monotherapy.(Initiation of study drug until study discontinuation, (up to approximately 24 months)))