A Study of APS03118 in Advanced Solid Tumors Harboring RET Mutations or Fusions

Study Overview
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Brief Summary
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This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antineoplastic activity of APS03118 administered orally in participants with RET-altered solid tumors.

Detailed Description
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After being informed about the study procedure and potential risks and benefits, all patients giving written informed consent will undergo a 4-week screening period to determine eligibility for study entry. The eligible participants will be enrolled using a rolling 6 dose escalation scheme to identify MTD and/or RP2D.

Official Title
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A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of APS03118 in Adult Patients With Unresectable Locally Advanced or Metastatic Solid Tumors Harboring RET Mutations or Fusions

Conditions
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RET-altered Solid Tumors

Intervention / Treatment
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* Drug: APS03118


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 18 years or older Have histological or cytological confirmation of unresectable locally advanced or metastatic solid tumors harboring oncogenic RET mutations or fusions confirmed by NGS. Site may identify patients with a RET-mutated or RET-fusion solid tumor before the formal screening. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Resolution of all toxic effects of prior therapies to Grade 1 or below according to NCI CTCAE version 5.0 (except alopecia or Grade 2 neuropathy); Patients with asymptomatic brain metastases if they have been previously treated, demonstrated no progression at least for 1 months before Screening, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before Screening Adequate organ function Exclusion Criteria: Have a locally advanced solid tumor that is a candidate for curative surgery treatment through radical surgery and/or radiotherapy. Have an active fungal, bacterial, and/or active untreated viral infection The patient has a serious pre-existing medical condition(s) Have received or will receive a COVID-19 vaccine within 1 month before the first dose of APS03118.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APS03118 Dose Escalation<br>APS03118 administered orally | Drug: APS03118<br>* Participant received APS03118 orally until evidence of unacceptable toxicity, progressed disease, consent withdrawal or with drawl from the study at the discretion of the investigator.<br>* Other names: APS03118 administrated orally;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of DLTs during Cycle 1 in dose-escalation cohorts |  | Within the 28 days of the first APS03118 dose for each patient | 
| The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D) | The MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 30%(<2/6) | Approximately 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events(AE) |  | Approximately 24 months | 
| Peak Plasma Concentration (Cmax) |  | Up to approximately 1 month | 
| Area under the plasma concentration versus time curve (AUC) |  | Up to approximately 1 month | 
| Time to Maximum Concentration (Tmax) |  | Up to approximately 1 month | 
| Degree of accumulation |  | Up to approximately 1 month | 
| Overall Response Rate (ORR) | As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | Up to approximately 24 months | 
| Duration of response (DOR) |  | Up to approximately 24 months | 
| Best of response (BOR) |  | Up to approximately 24 months | 
| Disease Control Rate (DCR) |  | Up to approximately 24 months | 
| Progress Free Survival (PFS) |  | Up to approximately 24 months |