Safety and Efficacy of Lacutamab in Patients With Relapsed/Refractory Peripheral T-cell Lymphoma That Express KIR3DL2

A Multi-center Phase Ib Trial Evaluating the Safety and Efficacy of Lacutamab in Patients With Relapsed/Refractory Peripheral T-cell Lymphoma That Express KIR3DL2

This is a multi-center phase Ib study, which evaluates the safety and efficacy of lacutamab monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma that express KIR3DL2.

This is an open-label, single-arm multicenter study. Eligible patients will be enrolled and will receive fixed dose of 750mg Lacutamab as a 1-hour IV infusion.

Inclusion Criteria:

1. Any subtype of PTCL;

2. Patients should have received at least one prior line of systemic therapy;

3. Patient with documented refractory, relapsed, or progressive disease. Patients must receive at least 2 cycles of prior line of systemic therapy (N-1). The patients who have withdrawn from prior (N-1) line of systemic therapy due to unacceptable toxicity must have received at least 2 cycles of prior (N-2) line of therapy;

4. KIR3DL2 expression (≥ 1%) based on central evaluation by IHC of either a newly acquired biopsy (preferred) or a tissue sample collected from a historical lymph node biopsy;

5. Presence of at least 1 target lesion on PET/CT scan at screening;

6. Male or Female, at least 18 years of age;

7. ECOG performance status ≤ 2;

8. The patient must have a minimum wash-out period of 3 weeks between the last dose of prior line of systemic therapy and first dose of lacutamab;

9. Patients should have recovered from clinically relevant adverse events related to prior therapy to ≤ grade 1. Certain toxicities will not be considered in this category (e.g., Grade 2 alopecia, peripheral neuropathy and/or endocrine end-organ failure being adequately managed by hormone replacement therapy);

10. Adequate baseline laboratory data:

    Hematology:

    • Hemoglobin >9 g/dL
    • Absolute neutrophil count (ANC) ≥1,000/µL,
    • Platelets ≥50,000/µL,

    Biochemistry:

    • Bilirubin ≤1.5 X upper limit of normal (ULN) or ≤3 X ULN for patients with Gilbert's disease,
    • Serum creatinine ≤1.5 X ULN,
    • Creatinine clearance ≥30 mL/min, assessed using the Cockcroft & Gault formula
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 X ULN;

11. Women of childbearing potential (WOCBP): Premenopausal females who had at least one menstrual cycle in the past 12 months and capable to become pregnant. They must have a negative serum beta-HCG pregnancy test result within seven days before start of treatment;

12. Women of childbearing potential and all men (and their female partners of childbearing potential) who are sexually active must agree to use adequate method of contraception at study entry, during treatment and for at least 9 months (270 days) following the last dose of study drug

13. Signed informed consent form prior to any protocol-specific procedure being performed.

Exclusion Criteria:

1. Treatment with > 8 lines of systemic therapies prior to enrollment. Consolidation therapy including stem cell transplant is not considered a line of therapy;
2. Patients having a life expectancy of less than 3 months;
3. Receipt of live vaccines within 4 weeks prior to treatment;
4. Known central nervous system (CNS) lymphoma involvement;
5. Prior treatment with lacutamab;
6. Concurrent enrollment in another clinical trial, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study;
7. Concomitant administration of radiotherapy or systemic anti-cancer therapy including but not restricted to: chemotherapy, biological agents or immunotherapy;
8. Autologous stem cell transplantation less than 3 months prior to enrollment;
9. Prior allogenic transplantation;
10. Patients who have undergone major surgery ≤ 4 weeks prior to study entry;
11. Patients with known NCI-CTCAE grade 3 or higher active systemic or cutaneous viral, bacterial, or fungal infection;
12. Patients who have active Hepatitis B or C virus infection confirmed by PCR;
13. Patients known or tested positive for human immunodeficiency virus (HIV);
14. Patients with a history of other malignancies during the past three years apart from the disease subject of this study. The following are exempt from the three-year limit: non_melanoma skin cancer, lymphomatoid papulosis, resected thyroid cancer, biopsy-proven cervical intraepithelial neoplasia, Ductal carcinoma in situ (DCIS) or cervical carcinoma in situ.
15. Pregnant or breastfeeding women;
16. Patients with congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria;
17. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment and/or comply with study protocol;
18. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document.