KEY TAKEAWAYS
- The phase Ib trial aimed to evaluate the safety and efficacy of ATRC-101, which targets a tumor-specific RNP, in advanced solid tumor pts.
- The primary objective was to determine the safety. Secondary objectives include PK, immunogenicity, the recommended dose for expansion, activity by RECIST1.1, and biomarker analyses in pre-tx and on-tx tumors.
- The study found ATRC-101 was well-tolerated and showed signs of anti-tumor activity, both alone and with P. The trial is ongoing.
ATRC-101 is a monoclonal antibody that targets a specific ribonucleoprotein complex(RNP) complex found in tumors. This antibody triggers innate and adaptive immune responses against tumors in preclinical models.
Researchers aimed to evaluate the safety and efficacy of ATRC-101, which targets a tumor-specific RNP, in advanced solid tumor patients(pts).
The study used different dosing intervals (3M or 2M weeks) and in combination with pembrolizumab (3P) for advanced solid tumor pts. Target expression for ATRC-101 was assessed using CAP-CLIA IHC assay. Pre-treatment(pre-tx) tumor biopsies were evaluated for target expression retrospectively or prospectively for the pts in this study. Enrollment in the 3M and 3P arms is open to pts who test positive for the target (RNP+ve) with an H-score of ≥ 50. The primary objective includes assessing safety. Secondary objectives include pharmacokinetics (PK), immunogenicity, determining the recommended dose for expansion, evaluating activity based on RECIST1.1 criteria, and conducting biomarker analyses on pre-treatment and on-treatment tumors.
The study analyzed various tumor types, including colorectal (CRC,28), ovarian (10), breast (9), melanoma (8), non-small cell lung (NSCLC, 6), head and neck squamous cell (3), urothelial (1), esophageal (1), and small bowel (1). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 22 (33%) pts and were related to ATRC-101 in 2 (3%). There were no treatment discontinuations or dose reductions related to ATRC-101. Among the 61 pts evaluated for efficacy according to RECIST1.1 criteria, there was 1 complete response (CR) in RNP-positive melanoma (3 P,10 mg/kg) and 1 partial response (PR) in RNP-positive NSCLC (3P, 30 mg/kg). Disease stabilization(SD) was observed in 24 pts (39%), including 9 CRC pts with highly refractory disease. Overall, there was evidence of an association between anti-tumor activity and target expression in the study.
The study found ATRC-101 was well-tolerated and showed signs of anti-tumor activity, both alone and with pembrolizumab. The trial is ongoing, and updated data will be presented, including the durability of disease control.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.2505#:~:text=
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04244552
Bartosz Chmielowski, Saravut John Weroha, Susanna Varkey Ulahannan, Deborah Blythe Doroshow, Frances Valdes, Tanios S. Bekaii-Saab, John D. Powderly, Alejandro Recio-Boiles, Jordan Berlin, Yan Xing, Sudha Khurana, Philippe Bishop, Steven J. Isakoff, and Benjamin Adam Weinberg. DOI: 10.1200/JCO.2023.41.16_suppl.2505 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 2505-2505.
