Clinical trial NCT05653869: A Study of APS03118 in Advanced Solid Tumors Harboring RET Mutations or Fusions
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: RET-altered Solid Tumors
Lead sponsor: Applied Pharmaceutical Science, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of DLTs during Cycle 1 in dose-escalation cohorts
timeFrame: Within the 28 days of the first APS03118 dose for each patient
measure: The maximum tolerated dose (MTD) and / or recommended Phase II dose (RP2D)
timeFrame: Approximately 15 months
Secondary outcomes:
measure: Adverse events(AE)
timeFrame: Approximately 24 months
measure: Peak Plasma Concentration (Cmax)
timeFrame: Up to approximately 1 month
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to approximately 1 month
measure: Time to Maximum Concentration (Tmax)
timeFrame: Up to approximately 1 month
measure: Degree of accumulation
timeFrame: Up to approximately 1 month
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Duration of response (DOR)
timeFrame: Up to approximately 24 months
measure: Best of response (BOR)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Progress Free Survival (PFS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
Study officials:
References: