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

Hepatosplenic T-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05475925
• Other study ID #: DR-01-ONC-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 13, 2022
• Est. completion date: December 2025

Study information

• Verified date: October 2023
• Source: Dren Bio
• Contact: Dren Central Contact
• Phone: 415-737-5277
• Email: clinops[@]drenbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 69
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (All Subjects):

1. =18 years of age.

2. Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document.

3. Sufficient key organ performance and coagulation.

4. 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.

5. Male subjects must agree to use acceptable effective method(s) of contraception.

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

6. Must have discontinued at least one prior line of systemic therapy.

7. 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.

8. Subjects must have failed at least two prior systemic regimens.

9. Availability of post-progression tissue sample or willingness to consent to a baseline biopsy.

10. Histologically confirmed diagnosis of a cytotoxic lymphoma by a hematopathologist (according to the WHO 2016 classification [Swerdlow 2016]).

11. For Part A only, evaluable disease is acceptable.

12. For Part B2 only:

Subjects must have radiographically measurable disease to be assessed by Lugano criteria. Subjects with primary cutaneous variants must have at least 1 measurable lesion that is evaluable using the Olsen criteria (Olsen 2021) or leukemic involvement that can be evaluated using a modified TPLL response criteria (Staber 2019).

Subjects with hepatosplenic disease or other variants that do not have measurable disease by Lugano criteria (Cheson 2014) may be eligible upon discussion with the Medical Monitor if they have identifiable leukemic involvement in BM or peripheral blood (meeting the CD8+ cytotoxic phenotype definition) that can be evaluated for response using a modified TPLL response criteria (Staber 2019), or skin involvement that can be evaluated using Olsen criteria (Olsen 2021).

Exclusion Criteria:

Disease-specific Exclusion Criteria; LGLL and ANKL:

1. 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:

2. Active systemic infection or severe localized infection requiring systemic antibiotics, antivirals or antifungals.

3. Active or suspected malignant central nervous system involvement.

4. Life-threatening, severe complications of malignancy (e.g., uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation).

5. Active known second malignancy.

6. Infection with human immunodeficiency virus (HIV) type 1 or 2 (HIV-1 or HIV-2).

7. 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.

8. History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II.

9. 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.

10. Any condition requiring hormonal therapy (except for contraception, hormone replacement therapy and hormonal prophylaxis for a prior malignancy).

11. 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.

12. 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).

13. Autologous HSCT within 40 days of C1D1, allogeneic HSCT within 90 days

14. Any immunosuppressive therapy for GVHD for subjects who are post allogeneic HSCT.

15. Major surgery within 28 days of C1D1 (requires more than local anesthesia or plexus blockade).

Related Conditions & MeSH terms

• Aggression
• Enteropathy-Associated T-Cell Lymphoma
• Extranodal NK/T Cell Lymphoma, Nasal Type
• Hepatosplenic T-cell Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Lymphoproliferative Disorders
• Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
• Panniculitis
• Subcutaneous Panniculitis-Like T-Cell Lymphoma

Intervention

Drug:
• DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Locations

Country	Name	City	State
Australia	Dren Investigational Site	Nedlands	Western Australia
Australia	Dren Investigational Site	Richmond	Victoria
France	Dren Investigational Site	Pierre-Bénite
France	Dren Investigational Site	Rennes
France	Dren Investigational Site	Toulouse
Spain	Dren Investigational Site	Barcelona
Spain	Dren Investigational Site	Salamanca
United States	Dren Investigational Site	Birmingham	Alabama
United States	Dren Investigational Site	Charlottesville	Virginia
United States	Dren Investigational Site	Columbus	Ohio
United States	Dren Investigational Site	Duarte	California
United States	Dren Investigational Site	Fairfax	Virginia
United States	Dren Investigational Site	Houston	Texas
United States	Dren Investigational Site	Jacksonville	Florida
United States	Dren Investigational Site	New York	New York
United States	Dren Investigational Site	Philadelphia	Pennsylvania
United States	Dren Investigational Site	Phoenix	Arizona
United States	Dren Investigational Site	Redwood City	California
United States	Dren Investigational Site	Rochester	Minnesota
United States	Dren Investigational Site	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Dren Bio	Novotech

Countries where clinical trial is conducted

United States,  Australia,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0.		Up to 25 months
Primary	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)
Primary	Part A: To determine potential pharmacologically optimized dose/regimen for DR-01 in LGL leukemia and cytotoxic lymphoma populations as determined using an integrated assessment of efficacy, safety, PK/PD, and exposure-response relationships.		Up to 6 months
Primary	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