Polyspecific Antibodies in Lymphoproliferative T-cell Disorders

Inclusion Criteria:

1. Provide signed, written informed consent.

2. Is male or female, age ≥18 years old (at the time consent is obtained)

3. For Part 1: Has a histological diagnosis of the following relapsed or refractoryPTCL based on WHO 2022 classification of lymphoid neoplasms

• Intestinal T-cell and NK cell lymphoid proliferations and lymphomas (without NKcell neoplasms)

• Hepatosplenic T-cell lymphoma

• Anaplastic large cell lymphoma

• Nodal TFH cell lymphoma

• Other peripheral t-cell lymphomas For Part 2: The type of PTCL will be definedbased on SC review after completion of Part 1 and will be documented in theprotocol amendment

4. Had previously received 1 or more appropriate systemic therapies, including analkylating agent and/or anthracycline, for treatment of the current disease (radiation therapy alone would not be acceptable as previous therapy). Participantswith ALCL must have received prior brentuximab vedotin or be unable to receive itdue to allergy or intolerance.

5. Experienced disease progression during or after completion of most recent therapy orrefractory disease.

6. Has a measurable lesion by imaging: the longest diameter should be ≥1.5 cm for nodallesions and >1 cm for extra-nodal lesions.

7. Experienced a toxicity of prior therapy: Participants must have recovered to lessthan Grade 1 or to baseline from toxicity of prior chemotherapy or biologic therapyand must not have had major surgery, chemotherapy, radiation, or biologic therapywithin 2 weeks prior to beginning treatment. Note: Exceptions to this include events not considered to place the participant atunacceptable risk of participation in the opinion of the Investigator (e.g.,alopecia).

8. Has either unstained tissues (block or unstained slides) or stained slides andpathology report available for central review. If stained slides or unstained tissueare not available or insufficient, a fresh tumor tissue sample is mandatory forcentral pathology. Central pathology confirmation is not required prior toenrollment.

9. Is able to provide a bone marrow aspirate and/or a biopsy no older than 3 months atscreening and agrees to undergo post-treatment bone marrow aspirate or biopsy whenrequired to confirm response.

10. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

11. Has life expectancy of >3 months.

12. Has an adequate hematological and organ function at screening, including:

• Hemoglobin ≥8.0 g/dL (prior transfusion is acceptable)

• Absolute neutrophil count (ANC) ≥1000 cells/mm3 (without growth factor supportwithin 7 days of ANC measurement)

• Platelet count ≥50,000 cells/mm3 (without growth factor support or transfusionwithin 7 days of platelets measurement)

• Creatinine clearance ≥30 mL/min

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × theupper limit of normal (ULN)

• Serum total bilirubin <2 × ULN OR <3 × ULN (for participants with Gilbert'sSyndrome)

13. Participants must be able to understand and sign an informed consent form.

14. All participants must use adequate contraception during participation in this studyand for 6 months following completing therapy.

Exclusion Criteria:

1. Is diagnosed with a bulky disease (≥10 cm).

2. Has known history or presence of central nervous system involvement by leukemia orlymphoma.

3. Has Mature T-cell and NK-cell leukemias (WHO 2022 criteria)

4. Has T-lymphoblastic leukemia/lymphoma (WHO 2022 criteria)

5. Has tumor-like lesions with T-cell predominance (WHO 2022 criteria)

6. Has Primary cutaneous T-cell lymphomas (WHO 2022 criteria)

7. Has any other active cancers, or history of treatment for invasive cancer ≤3 years. Note: Participants with stage I cancer who have received definitive local treatmentat least 3 years previously and are considered unlikely to recur are eligible. Allparticipants with previously treated in situ carcinoma (i.e., non-invasive) areeligible.

8. Received any of the following treatments prior to the first dose of studymedication:

• Systemic chemotherapy, targeted small molecule therapy, or radiation therapywithin 4 weeks (or 5 half-lives, whichever is shorter) before Cycle 1 Day 1.Participants that received local radiation therapy are eligible.

• Therapeutic anti-cancer antibodies <4 weeks

• Any investigational drug in the last 4 weeks prior

• Any major surgery or immunotherapy within 28 days

• Toxin immunoconjugates <4 weeks

• Nitrosoureas <6 weeks

• Allogeneic hematologic stem cell transplant within 3 months

• Adaptive cellular therapy such as autologous or donor natural killer cell or Tlymphocyte infusions within 90 days

• Systemic corticosteroids (prednisone or equivalent >10 mg daily) within 2 weeksprior to the start of therapy, or 12 weeks if given to treat graft versus hostdisease (GVHD), except for physiological replacement doses of cortisone acetateor equivalent

• Systemic treatment for GVHD (including but not limited to oral or parenteralcorticosteroids, ibrutinib, and extracorporeal phototherapy) within the last 12weeks

9. Is experiencing a toxicity (or AE) from prior anti-cancer treatment that has notresolved to Grade ≤1 or baseline.

10. Has a known infection with human immunodeficiency virus (HIV) or serologic statusreflecting active hepatitis B or C infection as follows:

• Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Participants with presence of HBcAb, but absence of HBsAg, areeligible only if hepatitis B virus (HBV) DNA is undetectable by an assay withsensitivity <20 IU/mL. If so, participants may either undergo regularlyscheduled monitoring of HBV DNA or less frequent monitoring of HBV DNA while onprophylactic antiviral medication as defined by regional standard of care.

• Presence of hepatitis C virus (HCV) antibody. Participants with presence of HCVantibody are eligible only if HCV RNA is undetectable.

11. Has a known active tuberculosis infection.

12. Has an active fungal, bacterial, and/or viral infection requiring systemic therapy.

13. Had a vaccination with a live vaccine within 35 days prior to the first dose ofLIS1.

14. If woman, is pregnant or nursing a child.

15. Has an active autoimmune disease or history of autoimmune disease that may relapseexcept for type I diabetes under control, hypothyroidism managed with hormonereplacement therapy, controlled celiac disease, and skin disease (vitiligo,psoriasis, etc.) not requiring systemic treatment.

16. Has a known history of interstitial lung disease, non-infectious pneumonitis,pulmonary fibrosis, acute lung disease, or dyspnea at rest or pulse oxymetrie < 92%at room air.

17. Has a clinically significant cardiovascular disease including the following:

• Myocardial infarction or unstable angina within 3 months before screening

• Congestive heart failure (New York Heart Association functional classificationIII-IV)

• History of clinically significant arrythmias

• QTcF > 470 msec

• History of Mobitz II second degree or third-degree heart block without apermanent pacemaker in place

• Uncontrolled hypertension as indicated by a minimum of 2 consecutive bloodpressure measurements showing systolic blood pressure >170 mm Hg and diastolicblood pressure >105 mmHg at screening

18. Has a cognitive impairment, active substance abuse, or psychiatric illness or socialsituations that, in the view of the Investigator, would preclude safe treatment orthe ability to give informed consent and limit compliance with study requirements.

19. Has a known history of drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepaticobstruction caused by stones, cirrhosis of the liver or portal hypertension.

20. Has a hemophilia or von Willebrand's disease.

21. Has any psychological, familial, sociological, or geographical conditions that donot permit compliance with the protocol.

22. Has a concurrent condition that, in the Investigator's opinion, would jeopardizecompliance with the protocol.

23. Are unable or unwilling to comply with study and/or follow-up procedures outlined inthe protocol.

24. For France, participants under legal protection (safeguard, guardianship,curatorship).

25. Is currently participating in another therapeutic clinical study.

26. Has a known hypersensitivity to polyclonal antibody.