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

Study 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.

Official Title
-----------------
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)

Conditions
-----------------
Relapsed or Refractory Peripheral T Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: AZD4205


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD4205 Group A<br>Group A: Open label AZD4205 at dose A, once daily (Phase 1) | Drug: AZD4205<br>* AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions<br>|
| Experimental: AZD4205 Group B<br>Group B: Open label AZD4205 at dose B, once daily (Phase 1) | Drug: AZD4205<br>* AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions<br>|
| Experimental: AZD4205 Group C<br>Group C: Open label AZD4205 at a selected dose, once daily (Phase 1) | Drug: AZD4205<br>* AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions<br>|
| Experimental: AZD4205 Group D<br>Group D: Open label AZD4205 at the RP2D, once daily (Phase 2) | Drug: AZD4205<br>* AZD4205 will be administered orally as capsules. AZD4205 treatment will be continued until disease progression or intolerant adverse reactions<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) based on CT scans per Lugano criteria | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | To evaluate the safety and tolerability of AZD4205 in patients with PTCL in terms of adverse events (AEs) | The first dose until 28 days after last dose | 
| Peak Plasma Concentration (Cmax) of AZD4205 |  | 1,8,15, 21 days after first dose | 
| Area under the plasma concentration versus time curve (AUC) of AZD4205 |  | 1,8,15, 21 days after first dose |