KEY TAKEAWAYS
- The phase I trial aimed to assess the safety and efficacy of TAS2940 in advanced solid tumors and HER2/EGFR aberrations pts.
- The primary objective of the Part 1 study is to determine the MTD and antitumor activity in Part 2. Secondary objectives include antitumor activity in Part 1.
- The study reported no serious side effects in dose escalation. The trial is still ongoing.
Aberrant expression of ERBB family receptors, such as human epidermal growth factor receptor 2(HER2) and epidermal growth factor receptor(EGFR), is associated with cancer. HER2-targeted therapies are effective in early and advanced HER2-positive breast cancer, but resistance develops. Around 4% of non–small cell lung cancer (NSCLC) patients (pts) have HER2 mutations, mostly exon 20 insertions (ex20ins). Current HER2/EGFR TKI treatments are ineffective in all pts with NSCLC and HER2 ex20ins.
TAS2940 is a promising new tyrosine kinase inhibitor(TKI) that can cross the blood-brain barrier and has shown efficacy against tumors with HER2/EGFR alterations.
Researchers aimed to assess the safety and efficacy of TAS2940 in advanced solid tumors and HER2/EGFR aberration pts.
The study included pts aged ≥18, with RECIST 1.1 or RANO criteria-measurable disease, ECOG 0/1, and organ function and excluded pts with unstable brain metastases. Part 1 (dose escalation) employs a Bayesian optimal interval design starting at 15 mg/kg orally QD (planned dose levels: 15, 30, 60, 120, 240, and 480 mg). After determining the recommended phase 2 dose, Part 2 (dose expansion) will enroll pts with NSCLC (Cohort A), HER2+ BC (Cohort B), recurrent/refractory GBM (Cohort C), or other solid tumors with EGFR/HER2 aberrations (Cohort D).
The primary objective is to determine the maximum tolerated dose (MTD) of TAS2940 in Part 1 and assess its antitumor activity in Part 2. Secondary objectives include evaluating antitumor activity in Part 1 and analyzing the safety and PK profile of TAS2940 in both parts.
The study plans to enroll approximately 142 pts, with around 42 in Part 1 and 100 in Part 2.
About 15 pts have been enrolled, and there have been no dose-limiting toxicities up to 240 mg QD. Recruitment is still ongoing.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.TPS3165
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04982926
Jordi Rodon Ahnert, David R. Spigel, Jill Kremer, Leah Jin, Karim Adnane Benhadji, Maciej Gil, and Benjamin Besse. DOI: 10.1200/JCO.2023.41.16_suppl.TPS3165 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) TPS3165-TPS3165
