Phase 1-2 Study of ASTX660 in Subjects With Advanced Solid Tumours and Lymphomas

Official Title

Phase 1-2 Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX660 in Subjects With Advanced Solid Tumours and Lymphomas

Summary:

This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and recommended dosing regimen, and to obtain preliminary efficacy, pharmacokinetic (PK), and target engagement data, in subjects with advanced solid tumours or lymphoma for whom standard life-prolonging measures are not available.

Trial Description

Primary Outcome:

  • Safety (Phase 1) - number of subjects with AEs, DLTs, abnormal clinical laboratory values or physical exam results
  • Efficacy (Phase 2) - antitumour activity assessed by objective response rate (ORR)
  • Efficacy (Phase 2) - antitumour activity assessed by disease control rate (DCR)
Secondary Outcome:
  • Pharmacokinetic outcome of concentration-time curve (AUC)
  • Pharmacokinetic outcome of maximum concentration (Cmax)
  • Pharmacokinetic outcome of minimum concentration (Cmin)
  • Pharmacokinetic outcome of time to maximum concentration (Tmax)
  • Pharmacokinetic outcome of samples over time
  • Pharmacokinetic outcome of samples over time
  • Pharmacokinetic outcome of analysis of ASTX660 metabolites if applicable
  • Efficacy - radiographic evaluation of tumour size using RECIST 1.1 criteria or another appropriate method if disease is not measureable using RECIST criteria
  • Assessment of target (cIAP1) engagement
ASTX660 is a synthetic small molecule dual antagonist of cellular inhibitor of apoptosis protein (cIAP) 1 and X-linked inhibitor of apoptosis protein (XIAP) that has been shown to have potent proapoptotic and tumour growth inhibitory activity in nonclinical models. ASTX660 has not been previously evaluated in human subjects. The Phase 1 portion of the study will determine the MTD, RP2D, and recommended dosing regimen. The Phase 2 portion will evaluate activity in selected tumour types. Subjects will continue to receive their assigned treatment throughout the study until the occurrence of disease progression, death, or unacceptable treatment-related toxicity, or until the study is closed by the sponsor. Tolerability and safety of study treatment will be evaluated throughout the study by collection of clinical and laboratory data. In Phase 2, antitumour response will be assessed using computed tomography (CT) or magnetic resonance imaging (MRI) scans or other appropriate disease evaluation methods. In subjects with solid tumours, response will be evaluated according to standard Response Evaluation Criteria in Solid Tumours (RECIST v1.1; Appendix 3). In subjects with DLBCL and PTCL, antitumour response will be evaluated according to the 2014 Lugano classification (Appendix 5). In subjects with CTCL, global overall response criteria will be used, based on skin, blood, node, and viscera assessments (Appendix 4).

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society