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

Phase 1

Recruiting

• Conditions: RET-altered Solid Tumors
• Interventions: Drug: APS03118

• Registration Number: NCT05653869
• Lead Sponsor: Applied Pharmaceutical Science, Inc.

Brief Summary

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

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.

Study Timeline

• Status Verified: 2022-11
• Study First Submitted: 2022-11-15
• Study First Submitted QC: 2022-12-08
• Study First Posted: 2022-12-16
• Study Start: 2023-02-06
• Last Update Submitted: 2023-06-14
• Last Update Posted: 2023-06-15
• Primary Completion: 2024-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Male or female patients aged 18 years or older
2. 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.
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
4. 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);
5. 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
6. Adequate organ function

Exclusion Criteria

1. Have a locally advanced solid tumor that is a candidate for curative surgery treatment through radical surgery and/or radiotherapy.
2. Have an active fungal, bacterial, and/or active untreated viral infection
3. The patient has a serious pre-existing medical condition(s)
4. Have received or will receive a COVID-19 vaccine within 1 month before the first dose of APS03118.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
APS03118 Dose Escalation	APS03118	APS03118 administered orally

Primary Outcome Measures

Name	Time	Method
The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D)	Approximately 15 months	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)
Incidence of DLTs during Cycle 1 in dose-escalation cohorts	Within the 28 days of the first APS03118 dose for each patient

Secondary Outcome Measures

Name	Time	Method
Duration of response (DOR)	Up to approximately 24 months
Best of response (BOR)	Up to approximately 24 months
Adverse events(AE)	Approximately 24 months
Disease Control Rate (DCR)	Up to 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
Progress Free Survival (PFS)	Up to approximately 24 months
Overall Response Rate (ORR)	Up to approximately 24 months	As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time to Maximum Concentration (Tmax)	Up to approximately 1 month
Degree of accumulation	Up to approximately 1 month

Trial Locations

Locations (1)

Shanghai Chest Hospital; 🇨🇳 Shanghai, Shanghai, China