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

Phase 1

Recruiting

• Conditions: LGLL - Large Granular Lymphocytic Leukemia; Primary Cutaneous Gamma-Delta T-Cell Lymphoma; Primary Cutaneous CD8+ Aggressive Epidermotropic 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
• Interventions: Drug: DR-01

• Registration Number: NCT05475925
• Lead Sponsor: Dren Bio

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

Detailed Description

Not available

Study Timeline

• Study Start: 2022-07-13
• Study First Submitted: 2022-07-21
• Study First Submitted QC: 2022-07-25
• Study First Posted: 2022-07-27
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-03
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

Not provided

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A Dose Escalation 1 mg/kg of DR-01	DR-01	Subjects in this arm will initially receive 1 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 6 mg/kg) thereafter for up to 25 cycles total.
Part A Dose Escalation 3 mg/kg of DR-01	DR-01	Subjects in this arm will initially receive 3 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 cycles total.
Part A Dose Escalation 6 mg/kg of DR-01	DR-01	Subjects in this arm will initially receive 6 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 cycles total.
Part A Dose Escalation 10 mg/kg of DR-01	DR-01	Subjects in this arm will initially receive 10 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 cycles total.
Part A Dose De-escalation 0.3 to <1 mg/kg of DR-01	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 at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 3 mg/kg) thereafter for up to 25 cycles total.
Part B Dose Expansion (Cohort B1) Optimized Dose/Regimen of DR-01	DR-01	Subjects in this arm will receive the pharmacologically optimized dose/regimen for LGL leukemia subjects determined in Part A. Depending on the selected dose/regimen, subjects will receive target dose at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing thereafter for up to 25 doses total.
Part B Dose Expansion (Cohort B2) Optimized Dose/Regimen of DR-01	DR-01	Subjects in this arm will receive the pharmacologically optimized dose/regimen for cytotoxic lymphoma subjects determined in Part A. Depending on the selected dose/regimen, subjects will receive target dose at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing thereafter for up to 25 doses total.

Primary Outcome Measures

Name	Time	Method
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: 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
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

Trial Locations

Locations (4)

Dren Investigational Site; 🇨🇳 Taipei, Taiwan

Dren Investigational Site 1; 🇰🇷 Seoul, Korea, Republic of

Dren Investigational Site 2; 🇰🇷 Seoul, Korea, Republic of

Dren Investigational Site 3; 🇰🇷 Seoul, Korea, Republic of