DR-01 for Leukemia and Lymphoma

Recruiting at 50 trial locations

Overseen By Dren Central Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dren Bio

Must not be taking: Systemic corticosteroids, Immunosuppressive drugs

Disqualifiers: Active infection, CNS malignancy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, DR-01 (a human anti-CD94 IgG1 monoclonal antibody), to determine its safety and effectiveness for certain blood cancers, specifically large granular lymphocytic leukemia and cytotoxic lymphomas. Researchers aim to understand how the drug behaves in the body and its potential to shrink tumors. The trial includes different groups to test various doses of DR-01, seeking the best treatment plan. Individuals who have not responded to other treatments and have either large granular lymphocytic leukemia or cytotoxic lymphomas may be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that DR-01 is being tested for safety in treating certain blood cancers, such as leukemia and lymphoma. DR-01 targets a specific part of immune cells called CD94.

In earlier studies, most participants tolerated DR-01 well. However, like any new treatment, some side effects occurred. Most were mild, such as fatigue or mild flu-like symptoms. Serious side effects were rare but could include low blood cell counts.

Since this trial is in the early stages, it primarily focuses on assessing the safety of DR-01 in humans. While the safety data appears promising, further testing is necessary to fully understand the risks. Participants will be closely monitored to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia and lymphoma?

Researchers are excited about DR-01 for leukemia and lymphoma because it offers a new approach compared to existing treatments like chemotherapy and targeted therapies. DR-01 is unique because it involves a dose-escalation strategy that allows for personalized dosing regimens to optimize effectiveness while minimizing side effects. Additionally, the trial explores multiple dosing schedules, which could provide more flexibility and potentially better outcomes for patients. These features make DR-01 a promising candidate to improve treatment efficacy and patient quality of life.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

Research shows that DR-01, which participants in this trial may receive, is a promising treatment for certain blood cancers, such as leukemia and lymphoma. As a monoclonal antibody, it targets specific proteins on cancer cells. Early findings indicate that DR-01 effectively targets a protein called CD94, found on some cancerous immune cells. This targeting may help stop the cancer cells from growing and spreading. Initial studies showed encouraging results in patients with certain types of leukemia and lymphoma. While more research is needed, these early results suggest that DR-01 could be an effective treatment option for these conditions. ^{1 2 3 5 6}

Who Is on the Research Team?

Wan-Jen Hong, MD

Principal Investigator

Dren Bio

Are You a Good Fit for This Trial?

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 vital organs are functioning well and my blood clots normally.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• DR-01

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Monoclonal antibodies represent a new treatment option for lymphoma, working through immunologic mechanisms to induce tumor lysis rather than causing DNA damage like traditional chemotherapy.

These antibodies have a favorable side effect profile and show significant effectiveness in treating chemoresistant lymphoma, suggesting they could be used alongside traditional therapies for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of monoclonal antibodies in the treatment of lymphomas. Hsu, JW., Dang, NH.[2013]

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 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]

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 have transformed cancer research and treatment by providing critical tools for understanding cancer cell behavior and are now essential in diagnosing and treating various cancers, particularly hematological malignancies.

This review specifically highlights the application of monoclonal antibodies in treating acute myeloid leukemia and mature B-cell neoplasms, showcasing their importance in modern cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in the treatment of hematologic malignancy. Ball, ED., Broome, HE.[2010]

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 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]

Monoclonal antibodies (MAbs) are being improved to enhance their effectiveness in treating hematologic malignancies, with three promising classes identified: unconjugated MAbs, drug-conjugated MAbs that deliver cytotoxic drugs directly to tumors, and radioactive immunotherapy that targets tumors with radiation.

Advancements in understanding how MAbs are metabolized and localized in the body are leading to the development of new antibody constructs that have better distribution profiles, potentially increasing their therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future of monoclonal antibodies in the treatment of hematologic malignancies. Reff, ME., Hariharan, K., Braslawsky, G.[2017]

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]

Citations

1. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper206053.html

980 Results from the First Phase 1 Clinical Study of DR-01, ... DR-01 is a non-fucosylated human IgG antibody targeting CD94, a receptor selectively expressed on cytotoxic terminal effector CD8+T cells, γδT cells, and NK ...

2. bloodcancerunited.org bloodcancerunited.org/research/award/phase-12-study-dr-01-anti-cd94-monoclonal-antibody-patients-large-granular

A phase 1/2 study of DR-01, an anti-CD94 monoclonal ... A Phase 1/2 trial is ongoing to assess the safety and efficacy of DR-01 in previously treated LGLL patients and cytotoxic lymphomas (NCT05475925) ...

3. youtube.com youtube.com/watch?v=WN4U-NrCeqU

DR-01, an anti-CD94 monoclonal antibody, in the treatment of ... Prof. Iyer notes that DR-01 has shown promising results in a Phase I ... The Leukemia & Lymphoma Society of Canada•8.8K views · 12:38 · Go ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12128193/

CD94+ Natural Killer cells potentiate pulmonary ischemia ... There was reduced killing of hypoxic epithelial cells with anti-human anti-CD94 monoclonal antibody treatment compared to isotype-matched control IgG treatment ...

5. withpower.com withpower.com/trial/phase-2-other-cd8nk-cell-driven-lymphoma-not-listed-above-6-2022-cf402

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 ...

6. bio-rad-antibodies.com bio-rad-antibodies.com/static/datasheets/mca22/human-cd94-antibody-dx22-mca2254.pdf

Datasheet: MCA2254 Product Details CD94 is expressed on natural killer (NK) cells and a subset of T lymphocytes. CD94 is found to associate with NKG2 to form a heterodimer which is involved in ...