A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas

1. Subject who understood and voluntarily signed and dated an informed consent prior toany study-specific assessments/procedures being conducted;

≥ 18 years of age at the time of signing the informed consent form (ICF);

3. Subject is willing and able to adhere to the study visit schedule and other protocolrequirements;

4. Subject with histologically proven peripheral T-cell lymphoma according to thecriteria of the WHO classification 2017 or 2022 (subjects with mycosis fungoides,Sezary syndrome, lymphoblastic or large granular lymphocytic lymphoma will beexcluded). Tumor tissue (initial diagnosis or relapse) should be available forcentral pathology review and biological characterization;

5. Subject in relapse/refractory situation;

6. ECOG performance status 0 to 2, or 3 if thought to be related to lymphoma;

7. Adequate bone marrow function as defined by:

• Absolute Neutrophil Count ≥ 1,5 x 10^9/L (≥ 1 x 10^9/L if related to lymphoma)

• Platelets ≥ 75 x 10^9/L (≥ 50 x 10^9/L if related to lymphoma)

• Hemoglobin ≥ 8 g/dL;

8. Anticipated life expectancy at least 3 months;

9. Presence of disease specific criteria allowing response evaluation. Unless otherwisespecified, such criteria include:

10. Baseline fluorodeoxyglucose PET-scan demonstrating at least one positive (FDG-avid) lesion;

11. and at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cmin its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension;

12. Contraception:

• For women of childbearing potential (WOCBP): must have a negative result forpregnancy test, at screening and within 24 hours prior to initiating studytreatment. The WOCBP agree to abstain from becoming pregnant or breastfeeding,to remain abstinent (from heterosexual intercourse) or use at least one highlyeffective method of contraception and to refrain from donating eggs, during thetreatment period (including periods of treatment interruption) and for at leastthe delay described in the sub-protocol for the concerned molecules;

• For men of reproductive potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use at least a condom as method of contraceptionwith a non-pregnant female partner of childbearing potential or a pregnantfemale partner, and to refrain from donating sperm, during the treatment period (including periods of treatment interruption), and for at least the delaydescribed in the sub-protocol for the concerned molecules;

11. Subject covered by a social security system;

12. Subject who understands and speaks one of the country official languages unlesslocal regulation authorizes independent translators; Additional inclusion criteria specific to Origina-ly-T sub-study:

13. For anaplastic large cell lymphoma subjects: failed or ineligible or intolerant tobrentuximab vedotin. For extranodal NK/T-cells lymphoma: failed or ineligible orintolerant to asparaginase-containing regimen; Additional inclusion criteria specific to Golcaza sub-study:

14. Subject had local diagnosed (nodal) follicular helper T cell lymphoma according to WHO classification 2022 or ICC 2022 classification based on a surgical lymph node biopsy or needle core biopsy including any one of the following type:

• angioimmunoblastic type (AITL)

• follicular T cell type

• not otherwise specified (NOS);

14. ECOG performance status 0 to 1 (supersedes criterium 6 of the Master protocol);

15. Subjects must have an international normalized ratio (INR) < 1.5 x ULN andpartial thromboplastin time (aPTT) < 1.5 x ULN (for subjects not receiving therapy).Note: Subjects receiving therapy for a thromboembolic event that occurred > 3monthsprior to enrollment are eligible as long as they are on a stable regimen ofanticoagulation with warfarin, low-molecular weight heparin, or other approvedtherapeutic anticoagulation or antiplatelet regimen;

16. Contraception (supersedes criterium 10 of the Master protocol):

• For women of childbearing potential (WOCBP): must have a negative result forpregnancy test, 10 to 14 days prior to initiating study treatment and within 24hours prior to initiating study treatment. WOCBP agree to abstain from becomingpregnant or breastfeeding and to remain abstinent (refrain from heterosexualintercourse) or use two adequate methods of contraception, including at least onehighly effective method of contraception , at least 28 days before the first dose ofstudy treatment , during the treatment period (including periods of treatmentinterruption), and for at least 28 days after the last dose of golcadomide, and 6months after the last dose of azacitidine. Women must refrain from donating eggsduring this same period;

• For men: during the treatment period (including periods of treatment interruption),and for at least 28 days after the last dose of golcadomide and 3 months after thelast dose of oral 5-azacitidine male subjects must:

• With female partners of childbearing potential: use a condom associated with ahighly effective method of contraception or remain abstinent (refrain fromheterosexual intercourse)

• With pregnant female partners: use a condom or remain abstinent (refrain fromheterosexual intercourse) Men must refrain from donating sperm during this sameperiod;

Exclusion Criteria:

1. Evidence of central nervous system involvement by lymphoma;

2. Any significant medical conditions, laboratory abnormality or psychiatric illnesslikely to interfere with participation in this clinical study (according to theinvestigator's decision);

3. Uncontrolled systemic fungal, bacterial, or viral infection;

4. Known Hepatitis C Virus (HCV) or active Hepatitis B Virus (HBV) infection defined assubject with detectable viral load (respectively detectable viral RNA or detectableviral DNA);

5. Active malignancy other than the one treated in this research, unless the subjecthas been free of the disease for 2 years (subjects with a history of a completelyresected non-melanoma skin cancer or successfully treated for an in-situ carcinomaare eligible);

6. Use of any standard or experimental anti-cancer drug therapy within 28 days or aminimum of 5 half-lives of the drug, whatever the shortest prior to firstadministration of study drug;.

7. Subject taking corticosteroids within 14 days prior to first administration of studydrug, unless administered at a cumulated dose equivalent of prednisone ≤ 20mg /day (within these 14 days);

8. Subject with prior autologous hematopoietic cell transplantation (auto-HCT) ≤ 3months prior to starting investigational product(s). If subject had autologous SCT (Stem Cell Transplant) > 3 months prior to the start of investigational product(s),any unresolved (Grade > 1) autologous SCT-related toxicity;

9. Subject with prior allogeneic hematopoietic cell transplantation (allo-HCT) witheither standard or reduced intensity conditioning ≤ 3 months prior to startinginvestigational product(s). If subject had allogeneic SCT > 3 months prior to thestart of investigational product(s) and still has any unresolved situation including (Grade > 1) treatment-related toxicity and/or ongoing immunosuppressor therapyand/or more than mild (NIH consensus) chronic graft-versus-host disease;

10. Subject with major surgery ≤ 14 days prior to starting investigational product(s).Subjects must have recovered from any clinically significant effects of recentsurgery;

11. Subject who has received prior localized anticancer therapy (eg. radiotherapy [including palliative radiotherapy]) ≤ 14 days prior to starting investigationalproduct(s);

12. Known or suspected hypersensitivity to active substance or to any of the excipients;

13. Pregnant, planning to become pregnant, or lactating woman;

14. Person deprived of his/her liberty by a judicial or administrative decision; Exclusion criteria specific to Origina-ly-T sub-study:

15. Positive HIV test at screening, with the following exception: individuals with apositive HIV test at screening are eligible provided they are stable onantiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have anundetectable viral load, and have not had a history of opportunistic infectionattributable to HIV within the last 12 months

16. Impaired renal function (calculated CKP-EPI, MDRD or Cockcroft-Gault CreatinineClearance < 30 ml/min) or impaired liver function tests (serum total bilirubin level > 34 μmol/L), except in case of Gilbert's Syndrome, or documented liver orpancreatic involvement by lymphoma, serum transaminases (AST or ALT) > 3 uppernormal limits, unless elevated to up to 5 x ULN due to peripheral T-cells lymphoma);

17. Significant cardiovascular disease [e.g., Objective Class C or D heart diseases (cf.Classes of Heart Failure | American Heart Association)], myocardial infarctionwithin the previous 6 months, unstable arrhythmia, or unstable angina);

18. Prior exposure to PI3Kdelta inhibitor;

19. Known or suspected allergies, hypersensitivity, or intolerance to Roginolisib or itsexcipients;

20. Inability to swallow food or any condition of the upper gastrointestinal tract thatprecludes administration of oral medications;

21. Subjects with a diagnosis of cutaneous T-cell lymphoma (CTCL);

22. Prior solid organ transplantation;

Exclusion criteria specific to GolcAza sub-study:

15. Evidence of positive HTLV1 serology;

16. Positive HIV test at screening, with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to HIV within the last 12 months;

17. Impaired renal function (calculated CKD-EPI, MDRD or Cockcroft-Gault Creatinine Clearance < 30 ml/min) or impaired liver function tests (serum total bilirubin level > 34 μmol/L) except in case of Gilbert's Syndrome, or documented liver or pancreatic involvement by lymphoma, serum transaminases (AST or ALT) > 3 upper normal limits (except documented liver involvement by lymphoma);

18. Prior exposure to golcadomide;

19. Refractory to azacitidine;

20. Significant cardiovascular disease [e.g., Objective Class C or D heart diseases (cf. Classes of Heart Failure | American Heart Association)], myocardial infarction ≤ 3 months prior to starting golcadomide, unstable angina pectoris ≤ 3 months prior to starting golcadomide), or complete left bundle branch or bifascicular block), congenital long QT syndrome, QTcF ≥ 470 msec on screening, persistent or clinically meaningful ventricular arrhythmias;

21. Received strong CYP3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, moderate CYP3A inducers within 7 days prior to initiation of study treatment;

22. Vaccinated with live, attenuated vaccines within 6 months of enrollment;

23. Known or suspected allergies, hypersensitivity, or intolerance to azacitidine, golcadomide or its excipients;

24. Any known malabsorption syndrome or disease associated with malabsorption.