DR-01 for Leukemia and Lymphoma

Recruiting at41 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Dren Bio

Must not be taking: Systemic corticosteroids, Immunosuppressive drugs

Disqualifiers: Active infection, CNS malignancy, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called DR-01 to see if it is safe and effective for adults with specific blood cancers. The study will check if the drug can safely reach and affect cancer cells to stop their growth.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does mention that you cannot use certain medications like systemic corticosteroids above specific doses within 15 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug DR-01 for leukemia and lymphoma?

Monoclonal antibodies, like DR-01, have been shown to be effective in treating various blood cancers, including leukemia and lymphoma, by targeting specific proteins on cancer cells. They are known for their unique action and fewer side effects, making them suitable for older patients or those with other health issues. ^{1 2 3 4 5}

Is DR-01 safe for humans?

The research on non-fucosylated therapeutic antibodies, like DR-01, suggests they have a favorable safety profile and are well-tolerated in preclinical studies, indicating they may be safe for humans. ^{4 6 7 8 9}

What makes the drug DR-01 unique for treating leukemia and lymphoma?

DR-01 is a monoclonal antibody that targets CD94, a specific protein on immune cells, which is different from other treatments that may target more common proteins like CD20 or CD19. This unique targeting could potentially offer a new approach for treating leukemia and lymphoma by focusing on a less commonly targeted pathway. ^{9 10 11 12 13}

Research Team

Kimberley Dilley, MD, MPH

Principal Investigator

Dren Bio

Eligibility Criteria

Adults with large granular lymphocytic leukemia or cytotoxic lymphomas who have tried at least one other treatment can join this trial. They must be over 18, meet specific diagnostic criteria, and have a certain level of organ function. Women able to bear children and men must use effective birth control. People with HIV, hepatitis B/C, severe heart issues, recent major surgery or those on high-dose steroids are excluded.

Inclusion Criteria

I have cytotoxic lymphoma and meet specific criteria numbers 8, 9, and 10.

For Part A only, evaluable disease is acceptable.

My lymphoma diagnosis is confirmed by a specialist according to WHO standards.

Exclusion Criteria

I have a serious heart condition worse than NYHA Class II.

I do not have severe complications like uncontrolled bleeding or severe infections from my cancer.

I am on hormonal therapy not related to contraception, hormone replacement, or cancer prevention.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects receive DR-01 at various doses (0.3 to 10 mg/kg) with different regimens during the first month, followed by monthly dosing for up to 25 cycles

25 months

Multiple visits during the first month, monthly visits thereafter

Dose Expansion

Subjects receive the pharmacologically optimized dose/regimen determined in Part A for up to 25 doses

25 months

Multiple visits during the first month, monthly visits thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• DR-01 (Monoclonal Antibodies)

Trial Overview The study is testing DR-01's safety and effectiveness in treating certain blood cancers. It's the first time humans will try it (Phase 1/2). The trial involves multiple centers where participants' reactions to the drug are closely monitored for any signs of improvement in their condition.

Participant Groups

Group I: Part B Dose Expansion (Cohort B2) Optimized Dose/Regimen of DR-01 Experimental Treatment 1 Intervention

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.

Group II: Part B Dose Expansion (Cohort B1) Optimized Dose/Regimen of DR-01 Experimental Treatment 1 Intervention

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.

Group III: Part A Dose Escalation 6 mg/kg of DR-01 Experimental Treatment 1 Intervention

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.

Group IV: Part A Dose Escalation 3 mg/kg of DR-01 Experimental Treatment 1 Intervention

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.

Group V: Part A Dose Escalation 10 mg/kg of DR-01 Experimental Treatment 1 Intervention

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.

Group VI: Part A Dose Escalation 1 mg/kg of DR-01 Experimental Treatment 1 Intervention

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.

Group VII: Part A Dose De-escalation 0.3 to <1 mg/kg of DR-01 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Dren Bio

Lead Sponsor

Trials

6

Recruited

280+

Novotech Health Holdings Pte. Ltd.

Industry Sponsor

Trials

1

Recruited

330+

ProTrials Research Inc.

Collaborator

Trials

1

Recruited

70+

Novotech

Collaborator

Trials

2

Recruited

80+

Findings from Research

Antibody-based therapies represent a significant advancement in leukemia treatment, offering unique mechanisms of action and improved side effect profiles, making them suitable for older patients or those with other health issues.

A better understanding of the biological characteristics of antibodies and their target antigens has led to enhanced therapeutic applications of monoclonal antibodies in treating both acute and chronic leukemias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody therapy of acute and chronic leukemias. Cataland, SR., Lucas, M., Byrd, JC.[2019]

Monoclonal antibodies, such as rituximab and alemtuzumab, are safe and well-tolerated treatments for lymphoma, showing effective response rates in both indolent and aggressive forms of the disease.

Rituximab significantly improves disease-free and overall survival when added to CHOP chemotherapy for aggressive lymphomas, highlighting its efficacy as a first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy for lymphoma. Campbell, P., Marcus, R.[2019]

The defucosylated chimeric anti-CCR4 IgG1 antibody KM2760 demonstrated significantly enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to its fucosylated counterpart KM3060, showing higher efficacy in killing T-cell leukemia/lymphoma cells in vitro.

In mouse models, KM2760 not only exhibited superior antitumor activity against T-cell malignancies when human immune cells were present, but also showed unexpected effectiveness in murine models, suggesting it may work through a different mechanism in mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Niwa, R., Shoji-Hosaka, E., Sakurada, M., et al.[2020]

The novel DR5-targeting antibody-drug conjugate (ADC) Oba01 shows significant tumor-killing activity against acute lymphoblastic leukemia (ALL) in preclinical models, effectively inhibiting tumor cell proliferation and inducing cell death.

Oba01 has a favorable safety profile and excellent pharmacokinetic properties, demonstrating stability and tolerability in animal models, making it a promising candidate for clinical trials in patients with DR5-positive ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of a novel antibody-drug conjugate targeting DR5 for lymphoblastic leukemia therapy. Zhang, S., Zhou, D., Zheng, C., et al.[2021]

Non-fucosylated therapeutic antibodies show significantly enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to fucosylated antibodies, making them a promising option for improving cancer treatment efficacy.

A unique host cell line has been developed to produce stable, non-fucosylated antibodies, which could lead to more effective therapies at lower doses, with clinical trials currently in progress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-fucosylated therapeutic antibodies as next-generation therapeutic antibodies. Satoh, M., Iida, S., Shitara, K.[2020]

Monoclonal antibodies targeting hematopoietic differentiation antigens have limited effectiveness as standalone treatments for leukemia, but they can be enhanced by attaching them to protein toxins to create immunotoxins.

Recombinant immunotoxins have demonstrated high cytotoxicity against leukemia cells in laboratory studies and early-phase clinical trials, suggesting they could become important in leukemia treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotoxins for leukemia. Wayne, AS., Fitzgerald, DJ., Kreitman, RJ., et al.[2022]

The monoclonal antibody NU-B1 specifically targets a novel antigen on B-cell lineage cells, showing reactivity with 7.7% of healthy adult peripheral blood mononuclear cells and all tested cases of B-cell leukemias and lymphomas, indicating its potential utility in diagnosing these conditions.

NU-B1 does not react with other blood cell types, such as T-cells or myeloid leukemias, and its antigenic determinant is distinct from known CD molecules, suggesting it could be a valuable tool for immunophenotyping and classifying various leukemias and lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody NU-B1 reacts with novel antigen on human B cells in mantle and marginal zones distinct from known CD molecules. Matsuo, Y., Sugimoto, A., Kuwahara, K., et al.[2019]

Monoclonal antibodies have significantly advanced our understanding of leukocyte differentiation and the origins of leukemia and lymphoma, revealing that acute lymphoblastic leukemia (ALL) is heterogeneous and primarily of B cell origin, with at least six distinct subgroups identified.

Therapeutic trials using monoclonal antibodies, including those conjugated to radionuclides and toxins, show promise in treating leukemia and lymphoma, with preliminary data suggesting that purging autologous bone marrow with these antibodies may be an effective therapy with reduced toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunologic classification of leukemia and lymphoma. Foon, KA., Todd, RF.[2021]

Monoclonal antibodies have significantly advanced our understanding of leukocyte differentiation and the origins of leukemia and lymphoma, revealing that nearly all cases of non-T-acute lymphoblastic leukemia (ALL) are of B-cell origin and identifying at least six distinct subgroups of non-T-ALL.

Therapeutic trials using monoclonal antibodies, including those conjugated to toxins or drugs, show promise in treating leukemia and lymphoma, with methods like purging autologous bone marrow potentially offering effective therapies while reducing associated toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory and clinical applications of monoclonal antibodies for leukemias and non-Hodgkin's lymphomas. Foon, KA.[2019]

The study identified six major subtypes of non-T cell acute lymphoblastic leukemia (ALL) using monoclonal antibodies, highlighting the effectiveness of surface immunoglobulin (sIg) and B1 antigen as key markers for B-cell lineage.

In chronic leukemias and lymphomas, 80% of tumors were classified as B-cell lineage based on sIg, and the study revealed distinct surface marker characteristics in Japanese cases compared to Western cases, suggesting potential differences in disease presentation and classification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody studies in B(non-T)-cell malignancies. Shimoyama, M., Minato, K., Tobinai, K., et al.[2007]

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Antibody therapy of acute and chronic leukemias. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy for lymphoma. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of a novel antibody-drug conjugate targeting DR5 for lymphoblastic leukemia therapy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Non-fucosylated therapeutic antibodies as next-generation therapeutic antibodies. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Immunotoxins for leukemia. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Monoclonal antibody NU-B1 reacts with novel antigen on human B cells in mantle and marginal zones distinct from known CD molecules. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Immunologic classification of leukemia and lymphoma. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Laboratory and clinical applications of monoclonal antibodies for leukemias and non-Hodgkin's lymphomas. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Monoclonal antibody studies in B(non-T)-cell malignancies. [2007]