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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05475925




Registration number
NCT05475925
Ethics application status
Date submitted
21/07/2022
Date registered
27/07/2022
Date last updated
27/10/2023

Titles & IDs
Public title
A Study of DR-01 in Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas
Scientific 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
Secondary ID [1] 0 0
DR-01-ONC-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
LGLL - Large Granular Lymphocytic Leukemia 0 0
Primary Cutaneous T-Cell Lymphoma - Category 0 0
Primary Cutaneous CD8-Positive Aggressive Epidermotropic T-Cell Lymphoma 0 0
Hepatosplenic T-cell Lymphoma 0 0
Subcutaneous Panniculitis-Like T-Cell Lymphoma 0 0
Aggressive NK Cell Leukemia 0 0
Systemic EBV1 T-cell Lymphoma, if CD8 Positive 0 0
Hydroa Vacciniforme-Like Lymphoproliferative Disorder 0 0
Extranodal NK/T Cell Lymphoma, Nasal Type 0 0
Enteropathy-Associated T-Cell Lymphoma 0 0
Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma 0 0
Indolent Chronic Lymphoproliferative Disorder (CLPD) (CD8+ or NK Derived) of the GI Tract 0 0
Other CD8+/NK Cell Driven Lymphoma Not Listed Above 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Skin 0 0 0 0
Other skin conditions
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DR-01

Experimental: Part A Dose Escalation 1 mg/kg of 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.

Experimental: Part A Dose Escalation 3 mg/kg of 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.

Experimental: Part A Dose Escalation 6 mg/kg of 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.

Experimental: Part A Dose Escalation 10 mg/kg of 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.

Experimental: Part A Dose De-escalation 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 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.

Experimental: Part B Dose Expansion (Cohort B1) Optimized Dose/Regimen of 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.

Experimental: Part B Dose Expansion (Cohort B2) Optimized Dose/Regimen of 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.


Treatment: Drugs: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0.
Timepoint [1] 0 0
Up to 25 months
Primary outcome [2] 0 0
Part A: Safety and Tolerability. To determine the incidence and severity of dose limiting toxicities (DLTs) as defined by protocol specified DLT criteria.
Timepoint [2] 0 0
During First 28 days (Cycle 1)
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to 6 months
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
Up to 24 months

Eligibility
Key inclusion criteria
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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
69
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Dren Investigational Site - Richmond
Recruitment hospital [2] 0 0
Dren Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
3121 - Richmond
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
France
State/province [12] 0 0
Pierre-Bénite
Country [13] 0 0
France
State/province [13] 0 0
Rennes
Country [14] 0 0
France
State/province [14] 0 0
Toulouse
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Salamanca

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Dren Bio
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Novotech
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT05475925
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kimberley Dilley, MD, MPH
Address 0 0
Dren Bio
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dren Central Contact
Address 0 0
Country 0 0
Phone 0 0
415-737-5277
Fax 0 0
Email 0 0
clinops@drenbio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05475925