A Study of DR-01 in Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas

Sponsor

Dren Bio (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05475925

Collaborator

ProTrials Research Inc. (Other), Novotech (Other)

Enrollment

Locations

Arms

40.6

Anticipated Duration (Months)

6.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicenter, first-in-human, Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of DR-01 in adult patients with large granular lymphocytic leukemia or cytotoxic lymphomas

Condition or Disease	Intervention/Treatment	Phase
LGLL - Large Granular Lymphocytic Leukemia Primary Cutaneous T-Cell Lymphoma - Category Primary Cutaneous CD8-Positive Aggressive Epidermotropic T-Cell Lymphoma Primary Cutaneous Acral CD8-Positive T-Cell Lymphoma Hepatosplenic T-cell Lymphoma Subcutaneous Panniculitis-Like T-Cell Lymphoma Aggressive NK Cell Leukemia Systemic EBV1 T-cell Lymphoma, if CD8 Positive Hydroa Vacciniforme-Like Lymphoproliferative Disorder Extranodal NK/T Cell Lymphoma, Nasal Type Enteropathy-Associated T-Cell Lymphoma Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma Indolent Chronic Lymphoproliferative Disorder (CLPD) (CD8+ or NK Derived) of the GI Tract Other CD8+/NK Cell Driven Lymphoma Not Listed Above	Drug: DR-01	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

69 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Open-Label, First-In-Human, Multiple Expansion Cohort, Phase 1/2 Study to Evaluate the Safety and Efficacy of DR-01 in Adult Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas

Actual Study Start Date :

Jul 13, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A Dose Escalation (Cohort 1) 1 mg/kg of DR-01 Subjects in this arm will initially receive 1 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 6 mg/kg) thereafter for up to 25 doses total.	Drug: DR-01 DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Experimental: Part A Dose Escalation (Cohort 2) 3 mg/kg of DR-01 Subjects in this arm will receive initially receive 3 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 doses total.	Drug: DR-01 DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Experimental: Part A Dose Escalation (Cohort 3) 6 mg/kg of DR-01 Subjects in this arm will receive initially receive 6 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 doses total.	Drug: DR-01 DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Experimental: Part A Dose Escalation (Cohort 4) 10 mg/kg of DR-01 Subjects in this arm will receive initially receive 10 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 doses total.	Drug: DR-01 DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Experimental: Part B Dose Expansion (Cohort B1) RP2D of DR-01 Subjects in this arm will receive the recommended Phase 2 dose for LGLL subjects (determined in Part A) every 14 days for the first two doses, followed by monthly dosing thereafter for up to 25 doses total.	Drug: DR-01 DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Experimental: Part B Dose Expansion (Cohort B2) RP2D of DR-01 Subjects in this arm will receive the recommended Phase 2 dose for cytotoxic lymphoma subjects (determined in Part A) every 14 days for the first two doses, followed by monthly dosing thereafter for up to 25 doses total.	Drug: DR-01 DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Experimental: Part A Dose De-escalation (Cohort -1) 0.3 to <1 mg/kg of DR-01 This cohort would only be triggered should a DLT occur at Dose Level 1 or if recommended by the Safety Review Committee. Subjects in this arm would initially receive 0.3 to <1 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 3mg/kg) thereafter for up to 25 doses total.	Drug: DR-01 DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Outcome Measures

Primary Outcome Measures

Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0. [Up to 25 months]
Part A: Safety and Tolerability. To determine the incidence and severity of dose limiting toxicities (DLTs) as defined by protocol specified DLT criteria. [During First 28 days (Cycle 1)]
Part A: Max tolerated dose of DR-01 (if applicable). [Up to 1 month]
Part A: Recommended Phase 2 dose (RP2D) of DR-01 in LGL leukemia and cytotoxic lymphoma populations as determined by integrated assessment of target engagement/attainment, efficacy, safety, PK/PD, and exposure-response relationships. [Up to 6 months]
Part B: Overall Response Rate (ORR), defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR) based on disease-specific response criteria. [Up to 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥18 years of age.
Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document.
Sufficient key organ performance and coagulation.
Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least one ovary, and is <1 year postmenopausal) must agree to use a highly effective method of contraception from enrollment through at least 12 months after last dose of DR-01.
Male subjects must agree to use acceptable effective method(s) of contraception.

Subjects with LGLL must also meet inclusion criteria 6 and 7.

Must have discontinued at least one prior line of systemic therapy.
Additional immunophenotypic criteria must be met.

Disease-specific Inclusion Criteria (Cytotoxic Lymphomas):

Subjects with cytotoxic lymphomas must also meet inclusion criteria 8,9, and 10.

Subjects must have failed at least two prior systemic regimens.
Availability of post-progression tissue sample or willingness to consent to a baseline biopsy.
Histologically confirmed diagnosis of a cytotoxic lymphoma by a hematopathologist (according to the WHO 2016 classification [Swerdlow 2016]).
For Part B2: Subjects must have radiographically measurable disease.

Exclusion Criteria:

Disease-specific Exclusion Criteria; LGLL and ANKL:

A reactive LGL lymphocytosis to a viral infection or LGL associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

The following exclusion criteria apply to all subjects:

Active systemic infection or severe localized infection requiring systemic antibiotics, antivirals or antifungals.
Active or suspected malignant central nervous system involvement.
Life-threatening, severe complications of malignancy (e.g., uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation).
Active known second malignancy.
Infection with human immunodeficiency virus (HIV) type 1 or 2 (HIV-1 or HIV-2).
Hepatitis B infection (hepatitis B virus surface antigen [HBsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid). Subjects with HCV with undetectable virus after treatment are eligible.
History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II.
Use of systemic corticosteroids (e.g., >5 mg/day prednisone or equivalent for subjects with LGL leukemia (subjects on 20 mg prednisone or equivalent to treat LGL leukemia must be weaned within 28 days post C1D1 to 5 mg) and >10 mg/day prednisone or equivalent for subjects with cytotoxic lymphoma) within 15 days (except for prophylaxis for radiodiagnostic contrast reactions), or other non-biological immunosuppressive drugs within 15 days, prior to C1D1. Patients on stable prednisone ≤10 mg for documented rheumatologic/autoimmune conditions are exempted from this requirement.
Any condition requiring hormonal therapy (except for contraception, hormone replacement therapy and hormonal prophylaxis for a prior malignancy).
Any other medical or psychiatric condition, or laboratory abnormality that would increase the risk associated with study participation, in the opinion of the Investigator or Medical Monitor.
Toxicities from previous anticancer therapies must have resolved to baseline levels or to Grade 1 (except for alopecia, peripheral neuropathy, or hematologic parameters meeting inclusion criteria).
Autologous HSCT within 40 days of C1D1, allogeneic HSCT within 90 days
Any immunosuppressive therapy for GVHD for subjects who are post allogeneic HSCT.
Major surgery within 28 days of C1D1 (requires more than local anesthesia or plexus blockade).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dren Investigational Site	Duarte	California	United States	91010
2	Dren Investigational Site	Redwood City	California	United States	94063
3	Dren Investigational Site	New York	New York	United States	10021
4	Dren Investigational Site	Columbus	Ohio	United States	43210
5	Dren Investigational Site	Philadelphia	Pennsylvania	United States	19107
6	Dren Investigational Site	Houston	Texas	United States	77030
7	Dren Investigational Site	Charlottesville	Virginia	United States	22903
8	Dren Investigational Site	Fairfax	Virginia	United States	22031
9	Dren Investigational Site	Richmond	Victoria	Australia	3121
10	Dren Investigational Site	Nedlands	Western Australia	Australia	6009