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

RET-altered Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05653869
• Other study ID #: APS-RET-102
• Status: Recruiting
• Phase: Phase 1
• Start date: February 6, 2023
• Est. completion date: April 2025

Study information

• Verified date: November 2022
• Source: Applied Pharmaceutical Science, Inc.
• Contact: Jun Zhong, PhD
• Phone: +86 13820403158
• Email: zhongjun[@]apspharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: April 2025
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• RET-altered Solid Tumors

Intervention

Drug:
• APS03118
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.

Locations

Country	Name	City	State
China	Shanghai Chest Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Applied Pharmaceutical Science, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of DLTs during Cycle 1 in dose-escalation cohorts		Within the 28 days of the first APS03118 dose for each patient
Primary	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	Adverse events(AE)		Approximately 24 months
Secondary	Peak Plasma Concentration (Cmax)		Up to approximately 1 month
Secondary	Area under the plasma concentration versus time curve (AUC)		Up to approximately 1 month
Secondary	Time to Maximum Concentration (Tmax)		Up to approximately 1 month
Secondary	Degree of accumulation		Up to approximately 1 month
Secondary	Overall Response Rate (ORR)	As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Up to approximately 24 months
Secondary	Duration of response (DOR)		Up to approximately 24 months
Secondary	Best of response (BOR)		Up to approximately 24 months
Secondary	Disease Control Rate (DCR)		Up to approximately 24 months
Secondary	Progress Free Survival (PFS)		Up to approximately 24 months