A Phase I/II, Open-Label, Multicentre Study to Investigate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD4205 in Patients With Peripheral T Cell Lymphoma (PTCL)
Overview
- Phase
- Phase 1
- Intervention
- golidocitinib
- Conditions
- Relapsed or Refractory Peripheral T Cell Lymphoma
- Sponsor
- Dizal Pharmaceuticals
- Enrollment
- 171
- Locations
- 50
- Primary Endpoint
- Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a multinational, non-randomized, open-label, Phase 1/2 clinical study to evaluate the safety, tolerability and anti-tumor efficacy of AZD4205 as monotherapy in patients with peripheral T cell lymphoma (PTCL), who have relapsed from or are refractory/intolerant to standard systemic treatment.
Phase 1 part:
Around 20~40 patients will be subsequently enrolled into 2 different dose ascending cohorts. Additional 10~20 patients may be enrolled to further explore a selected dose defined by dose escalation cohorts.
Phase 2 part:
After the recommended phase 2 dose (RP2D) is defined, a phase 2 single-arm open-label pivotal study will be conducted to assess anti-tumor efficacy and safety of AZD4205 at RP2D in patients with refractory or relapsed PTCL.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Obtained written informed consent
- •Patients must have histologically confirmed peripheral T-cell lymphoma according to the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Tumor samples are required for central pathology review to confirm the diagnosis.
- •Patients must have measurable disease according to the Lugano criteria.
- •Patients should be transplant-ineligible upon their entry into this study, and must have relapsed after or been refractory/intolerant to ≥ 1 (but not \> 3) prior systemic therapy(ies) for PTCL.
- •Adequate bone marrow reserve and organ system functions.
Exclusion Criteria
- •Any unsolved toxicity \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy (except alopecia).
- •Active infections, active or latent tuberculosis.
- •Patients with severely decreased lung function.
- •History of heart failure or QT interval prolongation.
- •Central nervous system (CNS) or leptomeningeal lymphoma.
- •History of treatment with Janus kinase (JAK) or signal transducer and activator of transcription 3 (STAT3) inhibitor.
- •Patient has undergone an allogeneic stem cell transplant. Patient had autologous stem cell transplant within 6 months.
Arms & Interventions
golidocitinib Group A
Group A: Open label golidocitinib at dose A, once daily (Phase 1)
Intervention: golidocitinib
golidocitinib Group B
Group B: Open label golidocitinib at dose B, once daily (Phase 1)
Intervention: golidocitinib
golidocitinib Group C
Group C: Open label golidocitinib at a selected dose, once daily (Phase 1)
Intervention: golidocitinib
golidocitinib Group D
Group D: Open label golidocitinib at the RP2D, once daily (Phase 2)
Intervention: golidocitinib
Outcomes
Primary Outcomes
Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC)
Time Frame: Up to approximately 3 years
ORR is the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) based on CT scans evaluated by IRC per Lugano criteria.
Secondary Outcomes
- Part A and Part B: Number of Participants With Adverse Events(The first dose until 28 days after last dose, up to approximately 3 years)
- Part B: Duration of Response (DoR) Assessed by IRC(Up to approximately 3 years)
- Part B: Complete Response Rate (CRR) Assessed by IRC(Up to approximately 3 years)
- Part B: Progression Free Survival (PFS) Assessed by IRC(Up to approximately 3 years)
- Part B: Time to Response (TTR) Assessed by IRC(Up to approximately 3 years)
- Part A and Part B: ORR Assessed by Investigator(Up to approximately 3 years)
- Part A and Part B: DoR Assessed by Investigator(Up to approximately 3 years)
- Part A and Part B: CRR Assessed by Investigator(Up to approximately 3 years)
- Part A and Part B: PFS Assessed by Investigator(Up to approximately 3 years)
- Part B: TTR Assessed by Investigator(Up to approximately 3 years)
- Part A and Part B: Maximum Plasma Concentration (Cmax) of AZD4205(Cycle 1 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D).)
- Part A and Part B: Area Under the Plasma Concentration-time Curve From Zero to the Last Measurable Concentration (AUC0-t) of AZD4205(Cycle 1, Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D).)
- Part A and Part B: Cmax,ss, at Steady State of AZD4205(Cycle 2 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D).)
- Part A and Part B: AUCss, at Steady State of AZD4205(Cycle 2 Day 1 (each cycle = 21 days): 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours postdose (for Group A, B and C); 0 (predose), 1, 2, 4, 6, 8, and 24 hours postdose (for Group D).)