Abstract
Abstract CT059: Phase 1b trial Mipasetamab Uzoptirine (ADCT-601-102) dose escalation in patients with advanced bone and soft tissue sarcomas
Cancer research (Chicago, Ill.), Vol.84(7_Supplement), pp.CT059-CT059
04/05/2024
DOI: 10.1158/1538-7445.AM2024-CT059
Abstract
Abstract Background: AXL is a cell surface receptor tyrosine kinase widely expressed in solid tumors (ST), including sarcomas. ADCT-601 (Mipasetamab uzoptirine; Mipa) is an antibody-drug conjugate comprising a humanized anti-AXL antibody conjugated via a cleavable linker to SG3199 (pyrrolobenzodiazepine dimer cytotoxin). Mipa demonstrated antitumor activity in pre-clinical mice models of sarcoma, adrenocortical carcinoma and pancreatic cancer, and clinical activity in ST patients (pts) in its first-in-human trial. Here, we report initial clinical data in pts with advanced bone and soft tissue sarcomas treated in dose escalation with Mipa. Objective: To characterize the safety and tolerability of Mipa in pts with sarcoma indications who exhausted standard of care therapy. Method: This is a phase 1b, open-label, dose-escalation, dose expansion study of Mipa (NCT05389462; EudraCT: 2021-00566-18). Pts received Mipa every 3 weeks (Q3W) at escalating dose levels, in a 3+3 dose escalation design. Results: As of 04 December 2023, 18 sarcoma patients (15 [83%], soft tissue sarcoma [STS] and 3 [17%] bone sarcoma), unselected for AXL expression, with a median number of 3 prior lines of therapy (1-10), were enrolled in 4 different dose cohorts: 7.5mg, 11mg, 13mg and 15mg. Reasons for treatment discontinuation were disease progression (10 pts [55.6%]), adverse events (3 pts [16.7%]) and consent withdrawal (2 pts [11.1%]). Treatment emergent adverse events (TEAE) were seen in 17 pts (94.4%). Most common TEAE (all grades and relationship [≥20%]) were palmar-plantar erythrodysesthesia syndrome (7 pts [38.9%]); anemia (6 pts [33.3%]); rash maculopapular (5 pts [27.8%]); cheilitis and constipation (4 pts each [22.2%]). TEAE≥grade 3 were seen in 9 pts (50%). Most common TEAE≥grade 3 (≥10%) were GGT increase (2 pts [11.1%]). Two dose limiting toxicities were seen: cheilitis grade 2 and grade 3 at 15mg and 13mg respectively. Cutaneous reactions, all grades, are more prominent in higher doses. Maximum tolerated dose (MTD) has not been established. In 17 sarcoma pts evaluable per RECISTv1.1, best overall response was partial response (PR) (2 pts [11.8%]), including a confirmed PR; stable disease (SD) (8 pts [47.1%]); progressive disease (7 pts [41.2%]). Tumor reductions was observed at 7.5mg, 11mg and 13mg. By week 12, 6/17 pts (35.3%) did not demonstrate PD . Initial IHC staining showed AXL expression in all sarcoma baseline biopsies tested so far. Initial pharmacokinetic (PK) data indicate exposures with moderate to marked interpatient variability; rapid clearance with no accumulation by Cycle 2. Updated biomarkers and PK data will be presented. Conclusion: The MTD was not established. Due to the incidence of TEAE judged related to Mipa and the preliminary activity observed, 15mg was selected as the highest dose to be tested in a fixed dose Q3W regimen. The study continues to enroll to further optimize Mipa dosing regimen and in dose escalation with gemcitabine. Citation Format: Brian Andrew Van Tine, Christopher T. Chen, Victor Moreno, Elizabeth J. Davis, Maria J. de Miguel, Antoine Italiano, Esma Saada-Bouzid, Mohammed Milhem, Claudia Valverde, Sant P. Chawla, Abdul Rafeh Naqash, Louise Carter, Robin Jones, Ilaria Conti, Joe Boni, Karin Havenith, Yvan LeBruchec, Serafino Pantano, Jean-Yves Blay. Phase 1b trial Mipasetamab Uzoptirine (ADCT-601-102) dose escalation in patients with advanced bone and soft tissue sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT059.
Details
- Title: Subtitle
- Abstract CT059: Phase 1b trial Mipasetamab Uzoptirine (ADCT-601-102) dose escalation in patients with advanced bone and soft tissue sarcomas
- Creators
- Brian Andrew Van Tine - Washington University in St. LouisChristopher T. Chen - Palo Alto UniversityVictor Moreno - Hospital Universitario Fundación Jiménez DíazElizabeth J. Davis - Vanderbilt University Medical CenterMaria J. de Miguel - Hospital Universitario HM SanchinarroAntoine Italiano - Institut BergoniéEsma Saada-Bouzid - Centre Antoine LacassagneMohammed Milhem - University of IowaClaudia Valverde - Vall d'Hebron Hospital UniversitariSant P. Chawla - Sarcoma Oncology CenterAbdul Rafeh Naqash - University of OklahomaLouise Carter - The Christie NHS Foundation TrustRobin Jones - Royal Marsden NHS Foundation TrustIlaria ContiJoe BoniKarin Havenith - e-TherapeuticsYvan LeBruchec - Adc TherapeuticsSerafino Pantano - Adc TherapeuticsJean-Yves Blay
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.84(7_Supplement), pp.CT059-CT059
- DOI
- 10.1158/1538-7445.AM2024-CT059
- ISSN
- 1538-7445
- eISSN
- 1538-7445
- Language
- English
- Date published
- 04/05/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984649054702771
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