Inclusion Criteria:
1. Histologically confirmed R/R nodal PTCL which include subtypes T-follicular helper cell lymphoma (angioimmunoblastic T-cell lymphoma, follicular T-helper cell lymphoma, T-follicular helper cell lymphoma-not otherwise specified), anaplastic large cell lymphoma (ALCL; both ALK+ and ALK-) and peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). In the absence of a fresh biopsy, the most recent archival tumour tissue should be used and obtained between the last dose of the last prior cancer regimen and C1D1.
2. Confirmed R/R disease after at least one prior line of therapy containing a combination chemotherapy regimen. Monotherapies, such as corticosteroids are excluded. Prior exposure to an ADC (including brentuximab vedotin) is permitted, provided all ADC-related toxicities, including but not limited to peripheral neuropathy, have resolved to Grade ≤1 prior to study entry.
3. Is an individual of any sex/gender, ≥18 years of age at the time of providing documented informed consent.
4. Patients of childbearing potential willing to adhere to the contraceptive precautions.
5. The participant (or legally acceptable representative) has provided documented informed consent for the study.
Additional Categories
6. Has an ECOG performance status of 0 to 1 (unless attributable to lymphoma, in which case patients of performance status 2 are eligible) assessed within 7 days before registration.
7. Has an ejection fraction ≥45% as determined by either ECHO or GCBP.
8. HIV infected participants must have well controlled HIV on ART.
9. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy and have undetectable HBV viral load prior to enrolment.
11\. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
12\. Participants with a prior allogeneic haematopoietic stem cell transplant are eligible provided they are \>90 days post-transplant, have no evidence of acute or chronic graft-versus-host disease, and are not receiving systemic immunosuppressive therapy (except for low-dose corticosteroids equivalent to \<10 mg/day of prednisolone). Participants with a prior autologous haematopoietic stem cell transplant are eligible provided they are \>90 days post-transplant and meet organ function and haematological parameter criteria unsupported by growth factors or transfusions.
13\. Life expectancy \> 12 weeks. 14. Adequate organ function
Exclusion Criteria:
1. Any other type of lymphoma except nodal PTCL as listed above.
2. Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
3. Has QTcF prolongation of \>480 msec.
4. Has ongoing Grade \>1 peripheral neuropathy.
5. Has a demyelinating form of Charcot-Marie-Tooth disease.
6. HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
7. Patients with a current or past history of venous thromboembolism (VTE; pulmonary embolism/deep venous thrombosis) are permitted to study inclusion provided that there is no contraindication to receive VTE prophylaxis with either anticoagulation or antiplatelet therapy.
8. Has ongoing corticosteroid therapy (exceeding 10 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 28 days prior to enrolment.
9. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
Refer to Section 6.5 for information on COVID-19 vaccines.
10. Known intolerance to any of the study interventions and/or their excipients.
11. Received a strong inhibitor or inducer of CYP3A4 within 14 days prior to randomization or is expected to require chronic use of a strong CYP3A4 inhibitor or inducer during treatment with study intervention until 30 days after the last dose.
12. Received a strong modulator of CYP2D6 or P-gp within 14 days prior to randomization or is expected to require chronic use of a strong modulator of CYP2D6 or P-gp during treatment with study intervention until 30 days after the last dose
13. Is receiving an investigational agent or has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
14. Known additional malignancy that is progressing or has required active treatment within the past 2 years.
15. Known active CNS lymphoma. CNS staging at diagnosis with MRI brain/spine and CSF analysis is not mandatory and only required if there is a clinical suspicion of CNS involvement.
16. Active infection requiring systemic therapy.
17. Concurrent active HBV (defined as HBsAg positive and detectable HBV DNA) and HCV (defined as anti-HCV antibody positive and detectable HCV RNA) infection.
18. History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
19. History of solid organ transplant within 2 years of study enrollment.
20. Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
