Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8)

Phase 1

Completed

• Conditions: Relapsed or Refractory Peripheral T Cell Lymphoma
• Interventions: Drug: golidocitinib

• Registration Number: NCT04105010
• Lead Sponsor: Dizal Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-10
• Study First Submitted: 2019-09-18
• Study First Submitted QC: 2019-09-24
• Study First Posted: 2019-09-26
• Primary Completion: 2023-10-12
• Study Completion: 2024-02-22
• Results First Submitted: 2025-01-20
• Status Verified: 2025-04
• Results First Submitted QC: 2025-04-03
• Last Update Submitted: 2025-04-03
• Results First Posted: 2025-04-04
• Last Update Posted: 2025-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 171

Inclusion Criteria

1. Obtained written informed consent
2. 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.
3. Patients must have measurable disease according to the Lugano criteria.
4. 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.
5. Adequate bone marrow reserve and organ system functions.

Exclusion Criteria

1. Any unsolved toxicity > Common Terminology Criteria for Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy (except alopecia).
2. Active infections, active or latent tuberculosis.
3. Patients with severely decreased lung function.
4. History of heart failure or QT interval prolongation.
5. Central nervous system (CNS) or leptomeningeal lymphoma.
6. History of treatment with Janus kinase (JAK) or signal transducer and activator of transcription 3 (STAT3) inhibitor.
7. Patient has undergone an allogeneic stem cell transplant. Patient had autologous stem cell transplant within 6 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
golidocitinib Group A	golidocitinib	Group A: Open label golidocitinib at dose A, once daily (Phase 1)
golidocitinib Group B	golidocitinib	Group B: Open label golidocitinib at dose B, once daily (Phase 1)
golidocitinib Group C	golidocitinib	Group C: Open label golidocitinib at a selected dose, once daily (Phase 1)
golidocitinib Group D	golidocitinib	Group D: Open label golidocitinib at the RP2D, once daily (Phase 2)

Primary Outcome Measures

Name	Time	Method
Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC)	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 Outcome Measures

Name	Time	Method
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).	Maximum observed plasma concentration (ng/mL) at steady state, obtained directly from the observed concentration versus time data. Calculated for the multiple doses.
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).	Area under the plasma concentration-time curve from time zero to the last quantifiable time point at steady state, calculated by the linear up/log down rule
Part B: Complete Response Rate (CRR) Assessed by IRC	Up to approximately 3 years	CRR is the percentage of patients with at least one visit response of CR based on CT scans evaluated by IRC per Lugano criteria.
Part A and Part B: DoR Assessed by Investigator	Up to approximately 3 years	DoR is the time from the date of first documented response until the date of documented progression or death due to any cause. Documented response and progression are both identified based on CT and/or PET scans evaluated by investigator per Lugano criteria.
Part A and Part B: CRR Assessed by Investigator	Up to approximately 3 years	CRR is the percentage of patients with at least one visit response of CR based on CT and/or PET scans evaluated by investigator per Lugano criteria.
Part B: TTR Assessed by Investigator	Up to approximately 3 years	TTR is the time from the date of first dosing to the time of the initial response of PR or CR. Response is identified based on CT scans evaluated by investigator per Lugano criteria.
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	To evaluate the safety and tolerability of AZD4205 in patients with PTCL in terms of adverse events (AEs), such as number of participants with AEs
Part B: Duration of Response (DoR) Assessed by IRC	Up to approximately 3 years	DoR is the time from the date of first documented response until the date of documented progression or death due to any cause. Documented response and progression are both identified based on CT scans evaluated by IRC per Lugano criteria.
Part B: Progression Free Survival (PFS) Assessed by IRC	Up to approximately 3 years	PFS is the time from the date of first dosing until the date of objective disease progression or death (by any cause) regardless of whether the participant discontinues the study treatments. Progression is identified based on CT scans evaluated by IRC per Lugano criteria.
Part B: Time to Response (TTR) Assessed by IRC	Up to approximately 3 years	TTR is the time from the date of first dosing to the time of the initial response of PR or CR. Response is identified based on CT scans evaluated by IRC per Lugano criteria.
Part A and Part B: ORR Assessed by Investigator	Up to approximately 3 years	ORR is the percentage of patients with at least one visit response of CR or PR based on CT and/or PET scans evaluated by investigator per Lugano criteria.
Part A and Part B: PFS Assessed by Investigator	Up to approximately 3 years	PFS is the time from the date of first dosing until the date of objective disease progression or death (by any cause) regardless of whether the participant discontinues the study treatments. Progression is identified based on CT and/or PET scans evaluated by investigator per Lugano criteria.
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).	Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. Calculated for the single dose.
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).	Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear up/log down rule.

Trial Locations

Locations (50)

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Epworth Hospital; 🇦🇺 East Melbourne, Australia

St Vincent's Hospital Melbourne; 🇦🇺 Fitzroy, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Australia

St George Hospital; 🇦🇺 Kogarah, Australia

Royal Perth Hospital; 🇦🇺 Perth, Australia

Westmead Hospital; 🇦🇺 Westmead, Australia

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