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

NCT05475925 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DR-01-ONC-001
• Study Type: interventional
• Target: 200
• Locations: 9 countries
• Sites: 37

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

Conditions

Cytotoxic PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker); LGLL - Large Granular Lymphocytic Leukemia; Extranodal NK/T Cell Lymphoma, Nasal Type; Enteropathy-Associated T-Cell Lymphoma; Primary Cutaneous Gamma-Delta T-Cell Lymphoma; Hepatosplenic T-cell Lymphoma; Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma; Primary Cutaneous CD8+ Aggressive Epidermotropic 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; Cutaneous PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker)

Keywords

LGLL; Cytotoxic; Lymphoma; ANKL; EATL; MEITL; ENKL; HSTCL; Leukemia; SPTCL; ENKTL; CTCL; PTCL-NOS; TCL

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (7)

Part A Dose Escalation 1 mg/kg of DR-01

EXPERIMENTAL

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.

Drug: DR-01

Part A Dose Escalation 3 mg/kg of DR-01

EXPERIMENTAL

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.

Drug: DR-01

Part A Dose Escalation 6 mg/kg of DR-01

EXPERIMENTAL

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.

Drug: DR-01

Part A Dose Escalation 10 mg/kg of DR-01

EXPERIMENTAL

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.

Drug: DR-01

Part A Dose De-escalation 0.3 to <1 mg/kg of DR-01

EXPERIMENTAL

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.

Drug: DR-01

Part B Dose Expansion (Cohort B1) Optimized Dose/Regimen of DR-01

EXPERIMENTAL

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.

Drug: DR-01

Part B Dose Expansion (Cohort B2) Optimized Dose/Regimen of DR-01

EXPERIMENTAL

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.

Drug: DR-01

Interventions

DR-01 DRUG

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

Part A Dose De-escalation 0.3 to <1 mg/kg of DR-01; Part A Dose Escalation 1 mg/kg of DR-01; Part A Dose Escalation 10 mg/kg of DR-01; Part A Dose Escalation 3 mg/kg of DR-01; Part A Dose Escalation 6 mg/kg of DR-01; Part B Dose Expansion (Cohort B1) Optimized Dose/Regimen of DR-01; Part B Dose Expansion (Cohort B2) Optimized Dose/Regimen of DR-01

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.
• Must have discontinued at least one prior line of systemic therapy.
• Additional immunophenotypic and symptomatic criteria must be met.
• Subjects must have failed at least one 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 A only, evaluable disease is acceptable.
• For Part B2 only, evaluable by the following response criteria as documented during Screening:
• For cytotoxic PTCL-NOS, ENKTL, MEITL, EATL, SPTCL - Subjects must have radiographically measurable disease by computed tomography (CT) or CT/positron emission tomography (PET) scan defined as at least one node measuring \>1.5 cm or measurable extranodal lesion of at least 1.0 cm in longest diameter to be evaluated by Lugano criteria (Cheson 2014).
• For PCGDTCL, ET-CTCL, HVLPD, cytotoxic CuPTCL-NOS - Subjects with primary cutaneous variants must have at least 1 measurable lesion that is evaluable using the Olsen criteria (Olsen 2021) or have leukemic involvement that can be evaluated using modified TPLL response criteria (Staber 2019).
• For HSTCL, ANKL, SysEBV TCL - Subjects with hepatosplenic disease without measurable disease by Lugano criteria (Cheson 2014) or leukemic involvement in BM or peripheral blood that is evaluable for response using a modified TPLL response criteria (Staber 2019).

You may not qualify if:

• A reactive LGL lymphocytosis to a viral infection or LGL associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• 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 at prohibited dose levels within 15 days prior to C1D1 (except for prophylaxis for radiodiagnostic contrast reactions and study-defined premedication) or use of other non-biological immunosuppressive drugs within 15 days or 5 half-lives (whichever is less) prior to C1D1.
• 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.
• 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).

Sponsors & Collaborators

• Dren Bio: lead

Study Sites (37)

Dren Investigational Site

Birmingham, Alabama, 35233, United States

RECRUITING

Dren Investigational Site

Duarte, California, 91010, United States

RECRUITING

Dren Investigational Site

Irvine, California, 92612, United States

RECRUITING

Dren Investigational Site

Redwood City, California, 94063, United States

RECRUITING

Dren Investigational Site

New Haven, Connecticut, 06519, United States

RECRUITING

Dren Investigational Site

Tampa, Florida, 33612, United States

RECRUITING

Dren Investigational Site

Boston, Massachusetts, 02114, United States

RECRUITING

Dren Investigational Site 1

New York, New York, 10021, United States

RECRUITING

Dren Investigational Site 2

New York, New York, 10032, United States

NOT YET RECRUITING

Dren Investigational Site

Columbus, Ohio, 43210, United States

RECRUITING

Dren Investigational Site 2

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Dren Investigational Site

Houston, Texas, 77030, United States

RECRUITING

Dren Investigational Site

Charlottesville, Virginia, 22903, United States

RECRUITING

Dren Investigational Site

Fairfax, Virginia, 22031, United States

RECRUITING

Dren Investigational Site

Seattle, Washington, 98109, United States

RECRUITING

Dren Investigational Site

Clayton, Victoria, 3168, Australia

RECRUITING

Dren Investigational Site

Richmond, Victoria, 3121, Australia

RECRUITING

Dren Investigational Site

Nedlands, Washington, 6009, Australia

RECRUITING

Dren Investigational Site

Pierre-Bénite, 69310, France

RECRUITING

Dren Investigational Site

Rennes, 35000, France

RECRUITING

Dren Investigational Site

Toulouse, 31059, France

RECRUITING

Dren Investigational Site

Berlin, 10117, Germany

RECRUITING

Dren Investigational Site

Cologne, 50937, Germany

RECRUITING

Dren Investigational Site

Leipzig, 04103, Germany

RECRUITING

Dren Investigational Site 1

Hong Kong, Hong Kong, Hong Kong

RECRUITING

Dren Investigational Site 2

Hong Kong, Hong Kong

RECRUITING

Dren Investigational Site

Bologna, 40126, Italy

RECRUITING

Dren Investigational Site 1

Busan, South Korea

RECRUITING

Dren Investigational Site 2

Busan, South Korea

RECRUITING

Dren Investigational Site

Goyang-si, South Korea

RECRUITING

Dren Investigational Site 1

Seoul, South Korea

RECRUITING

Dren Investigational Site 2

Seoul, South Korea

RECRUITING

Dren Investigational Site 3

Seoul, South Korea

RECRUITING

Dren Investigational Site

Barcelona, 08035, Spain

RECRUITING

Dren Investigational Site

Salamanca, 37007, Spain

RECRUITING

Dren Investigational Site

Tainan, Taiwan

RECRUITING

Dren Investigational Site

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Leukemia, Large Granular Lymphocytic; Subcutaneous panniculitis-like T-cell lymphoma; Lymphoma, Extranodal NK-T-Cell; Enteropathy-Associated T-Cell Lymphoma; Lymphoma; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, T-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin

Study Officials

• Wan-Jen Hong, MD

  Dren Bio

  STUDY DIRECTOR

Central Study Contacts

Dren Central Contact

CONTACT

415-737-5277; DR-01-ONC-001_inquiries@drenbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2022
• First Posted: July 27, 2022
• Study Start: July 13, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); TW (2); AU (3); IT (1); US (15); FR (3); KR (6); ES (2); HK (2)