In short
Clinical trials are investigating Apl-101 in people with advanced solid tumors, including non-small cell lung cancer and central nervous system tumors. These studies are looking at safety, the best dose, and early signs of how well the treatment works in tumors with MET changes.
Key points
- Apl-101 is being studied in clinical trials for advanced solid tumors with MET changes, including non-small cell lung cancer and central nervous system tumors. The main study is a Phase 1 and Phase 2 trial that looked at safety, tolerability, dose finding, and early signs of benefit. In Phase 1, the researchers focused on dose-limiting toxicities, the maximum tolerated dose, and the recommended Phase 2 dose. In Phase 2, they measured objective response rate, which shows how many tumors shrink or disappear. The trial also includes Apl-101 used by itself and as an add-on treatment in some NSCLC patients with EGFR resistance and MET amplification.
Trial overview
The available study is an interventional trial of Apl-101 in advanced MET-expressing solid tumors, including non-small cell lung cancer and central nervous system tumors. The study is designed to evaluate safety, effectiveness, and the best dose for later testing.
Who the trials include
The trial includes people with selected advanced solid tumors and NSCLC with MET aberrations. The Phase 2 part also targets people with NSCLC harboring MET exon 14 skipping mutations, MET amplification, or EGFR activating mutations with acquired resistance and MET amplification after prior EGFR inhibitor treatment.
The study also includes pan-cancers, which means different kinds of solid tumors grouped together if they share the same MET change. Primary CNS tumors with MET alterations are also part of the planned Phase 2 evaluation.
Study phases and goals
This study has a completed Phase 1 part and a Phase 2 part. Phase 1 aimed to assess overall safety and tolerability, find dose-limiting toxicities, identify the recommended Phase 2 dose, and collect early pharmacokinetic data, which means how the body absorbs and handles the treatment.
Phase 2 is focused on how well Apl-101 works as a monotherapy, meaning used alone, in several MET-driven cancer groups. It also studies Apl-101 as an add-on to an EGFR inhibitor in a specific group of NSCLC patients who developed acquired resistance with MET amplification.
What the trials measure
One key Phase 1 endpoint is the maximum tolerated dose (MTD), which is the highest dose that can be given with acceptable side effects. The study also measures dose-limiting toxicities, sustained Grade 2 adverse events, dose reductions, dose interruptions, delayed toxicities, and other adverse events to help choose the recommended Phase 2 dose.
In Phase 2, the main outcome is objective response rate (ORR), which combines complete response and partial response. Tumor response is judged by independent review using RECIST v1.1 for many solid tumors and RANO criteria for CNS tumors, with other tumor-specific criteria used when needed.
Treatment approaches being tested
Apl-101 is being studied as a single treatment in several cancer groups with MET changes. This includes NSCLC with MET exon 14 skipping mutations, NSCLC with MET amplification, pan-cancers with MET amplification, pan-cancers with MET fusion, primary CNS tumors with MET alterations, and pan-cancers with wild-type MET plus HGF and MET overexpression.
The trial also studies Apl-101 together with an EGFR inhibitor for people with NSCLC who first responded to EGFR inhibitor treatment, then later had disease progression and MET amplification. In this setting, the study looks at whether adding Apl-101 may help after resistance has developed.
Trial status and size
The trial is listed as authorised and is an interventional study. The enrollment number is 497, which means the study planned to include 497 participants.