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

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

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.

Study Overview

• Status: Recruiting
• Conditions: RET-altered Solid Tumors
• Intervention / Treatment: Drug: APS03118

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 Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jun Zhong, PhD; Phone Number: +86 13820403158; Email: zhongjun@apspharm.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Shun Lu, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APS03118 Dose Escalation; APS03118 administered orally	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.; Other Names: APS03118 administrated orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Applied Pharmaceutical Science, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: APS-RET-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No