This is a modular dose confirmation and expansion study. The core study design is to assess the efficacy of AZD4573, administered as monotherapy or combination therapy, to participants with either r/r PTCL or r/r cHL and to confirm the safety profiles and PK in these populations. Module 1 of this study will evaluate the efficacy, safety, and tolerability of AZD4573 monotherapy in participants with r/r PTCL or r/r cHL. If AZD4573 monotherapy is found to have promising anti-tumour efficacy in Module 1, an AZD4573 monotherapy Phase II expansion may be added via a substantial protocol amendment.

Module 1 will consist of two r/r PTCL cohorts and one cHL cohort; and each cohort includes 21 participants. A comprehensive initial review of all safety and PK/PD data will be conducted in approximately the first 6 participants of each cohort (safety run-in), with separate Safety Review Committees (SRCs) for each cohort executed independently. The safety assessment will be undertaken by the SRC. Each cohort will have a separate dose confirmation, assessed independently by the SRC, to assess safety and PK/PD data compared to the known profiles in the first time in human study (Study D8230C00001) lymphoma population. These SRC reviews will confirm whether the recommended phase II dose for lymphoma (IV infusion 12 mg once weekly, including intra-participant ramp-up) is safe and tolerable or if additional dose optimisation is indicated at a revised dose and/or schedule. All cohorts can be opened and delivered independently of each other.

Inclusion Criteria:

• Participants who are diagnosed with one of the following, as defined by the World Health Organisation:

  • Peripheral T-cell Lymphoma
  • Classical Hodgkin Lymphoma

• Eastern Cooperative Oncology Group performance status of ≤ 2.

• Must have received at least 1 prior line of therapy for the treatment of current disease and have documented relapsed or refractory active disease requiring treatment, defined as:

  • Recurrence of disease after response to prior line(s) of therapy, or
  • Progressive disease after completion of or on the treatment regimen preceding entry into the study, or
  • Disease which did not achieve an objective response (CR or PR).

• Uric acid level < ULN at screening. If hyperuricaemia is present at screening, SoC therapy should be administered (including IV fluid and rasburicase or allopurinol) to reduce the uric acid levels to < ULN before the start of study intervention.

• Willing and able to participate in all required evaluations and procedures in this study protocol including receiving IV administration of study drug and being admitted, if required, for at least 24 hours during study drug administration.

• Fresh tumour tissue or archival tumour tissue must be confirmed to be available at screening.

• Adequate haematologic function at screening.

• PTCL Only: All participants with PTCL must be willing and able to provide baseline bone marrow aspirate and/or biopsy no older than 3 months and agree to undergo post-treatment bone marrow biopsy when required to confirm response.

Additional Module 1 Inclusion Criteria

Prior lines of therapy:

• PTCL: Participants must have failed at least 1 prior therapy for the treatment of PTCL.

  • Non NK-PTCL (Cohort 1): Prior therapy must have included an alkylating agent and/or anthracycline. In addition, ALCL participants must have received brentuximab vedotin (BV) as part of prior therapy.
  • NKTCL (Cohort 2): Prior treatment must have included a platinum agent and/or asparaginase.

• cHL (Cohort 3): Participants must have failed at least 2 prior therapies for the treatment of cHL (including BV and anti-PD1) except where unable to receive BV or anti-PD1 due to neuropathy or autoimmune disease.

• Presence of at least 1 radiographically measurable, FDG-avid lymphoma disease lesion > 1.5 cm (according to the Lugano (2014) criteria [Cheson et al 2014]).

Exclusion Criteria

Type of Participant and Disease Characteristics:

• PTCL only: Presence of bulky disease (defined as largest lymphoma lesion ≥ 10 cm) or a LDH value > 3 x ULN.
• PTCL only: Diagnosis of any of the following: Lymphoblastic/precursor T-cell lymphoma or leukaemia; T-cell prolymphocytic leukaemia; T-cell large granular lymphocytic leukaemia; Cutaneous T-cell lymphoma (eg, primary cutaneous type ALCL, mycosis fungoide/Sezary syndrome).

Medical Conditions:

• With the exception of alopecia and neuropathy, presence of any unresolved non haematological toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment.

• Presence of, or history of, CNS lymphoma, leptomeningeal disease, or spinal cord compression.

• History of prior non-haematological malignancy except for the following:

  • Malignancy treated with curative intent and with no evidence of active disease present for more than 1 year prior to screening and felt to be at low risk for recurrence by treating physician.
  • Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer.
  • Adequately treated carcinoma in situ without current evidence of disease.

• Any evidence of:

  • Severe or uncontrolled systemic disease (eg, severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]).
  • Current unstable or uncompensated respiratory or cardiac conditions.
  • Uncontrolled hypertension.
  • Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
  • IV anti-infective treatment within 1 week before first dose of study drug.

• Known history of infection with HIV.

• Serologic status reflecting active hepatitis B or C infection:

  • Participants who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative PCR result before enrolment. Those who are hepatitis B surface antigen positive or hepatitis B PCR-positive will be excluded.
  • Participants who are hepatitis C antibody positive will need to have a negative PCR result before enrolment. Those who are hepatitis C PCR-positive will be excluded.

• Any of the following cardiac criteria:

  • Resting QT interval corrected using Fridericia's formula (QTcF) ≥ 470 msec obtained from a single ECG.
  • Any clinically important abnormalities in rhythm (except for participants with a pacemaker in place), conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block).
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.

• Documented confirmation and ongoing treatment of adrenal gland insufficiency or pancreatitis.

• Undergone any of the following procedures or experienced any of the following conditions within 6 months prior to first dose:

  • Coronary artery bypass graft
  • Angioplasty
  • Vascular stent
  • Myocardial infarction
  • Angina pectoris
  • CHF (New York Heart Association Class ≥ 2)
  • Ventricular arrhythmias requiring continuous therapy
  • Atrial fibrillation, which is judged as uncontrolled by the treating physician
  • Haemorrhagic or thrombotic stroke, including transient ischemic attacks or any other CNS bleeding

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.