RET-altered Solid Tumors
Conditions
Brief summary
This is a Phase 1/1b, 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.
Interventions
DRUGAPS03118
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.
Sponsors
Applied Pharmaceutical Science, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to approximately 24 months | As assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) |
| 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 | — |
Countries
China
Outcome results
None listed