DTRM-555 / Zhejiang DTRM Biopharma - LARVOL DELTA

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=55 | Terminated | Sponsor: Zhejiang DTRM Biopharma | N=120 ➔ 55 | Active, not recruiting ➔ Terminated; Despite the efforts of our dedicated team and initial progress, we were unable to secure the necessary financial resources to continue the study. We appreciate the support and participation of all involved.

Enrollment change • Trial termination • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Zhejiang DTRM Biopharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Zhejiang DTRM Biopharma | Trial completion date: Mar 2024 ➔ Dec 2024 | Trial primary completion date: Mar 2024 ➔ Dec 2024

Combination therapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

Extended Abstract: New BTKi (SOHO 2022) - "It has also been studied in combination with idelalisib or entospletinib in CLL and other B-cell lymphomas though without clear benefi t for the combinations over monotherapy16,17. Tirabrutinib is approved in Japan for WM, lymphoplasmacytic lymphoma (LPL), and RRPCNSL, and in South Korea for RR-PCNSL18. TG-1701 is a selective covalent BTKi that has been studied as a monotherapy and in combination with ublituximab and umbralisib with preliminary results suggesting both effi cacy and manageable safety19. Orelabrutinib, another selective covalent BTKi, has been studied as a monotherapy in CLL in addition to other B-cell malignancies, also with favorable safety and effi cacy20,21 and it is approved in China for rel/ref CLL and MCL22. Finally, DTRMWXHS-12 is a covalent BTKi that uniquely is being studied in combination with everolimus and pomalidomide (triplet referred to as DTRM-555), given that this combination was determined to lead to synthetic lethality in both in vivo..."

IO biomarker • Chronic Lymphocytic Leukemia • CNS Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • FLT3 • IL2 • ITK • PLCG2

DTRMWXHS-12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: an open-label, multicenter, phase 1a/1b study. (PubMed, Am J Hematol) - "Our dose escalation study used an accelerated titration design and moved sequentially from single agent BTKi (DTRMWXHS-12), doublet (DTRMWXHS-12 + everolimus), and then to triplet therapy (DTRMWXHS-12 + everolimus + pomalidomide). Combining DTRMWXHS-12 with everolimus and pomalidomide is tolerable and shows clinical activity. Additional trials could confirm benefit of this all-oral combination therapy for relapsed/refractory lymphomas."

Combination therapy • Journal • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Immune Modulation • Lymphoma • Oncology

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Zhejiang DTRM Biopharma | Trial completion date: Mar 2022 ➔ Mar 2024 | Trial primary completion date: Mar 2022 ➔ Mar 2024

Combination therapy • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • BCL2

Safety and Tolerability Analysis of Melflufen plus Dexamethasone in Patients with Relapsed/Refractory MM (Oncology Learning Network) - P3, N=NA; OCEAN (NCT03151811); Sponsor: Oncopeptides AB; "'In the OCEAN study, safety and tolerability of melflufen [plus dexamethosone] was consistent with prior reports. Hematologic AEs were common but generally manageable with dose modifications. Despite a higher cytopenia frequency with melflufen, rates of concurrent grade 3/4 bleedings and infections were low and grade 3/4 infections were more common with pomalidomide,' concluded Dr Richardson..."

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[VIRTUAL] A Once Daily, Oral, Triple Combination of BTK Inhibitor, mTOR Inhibitor and IMiD for Treatment of Relapsed/Refractory Richter’s Transformation and De Novo Diffuse Large B-Cell Lymphoma (ASH 2020) - P1a/1b | "DTRM-555 is an optimized oral triple combination of a novel irreversible BTKi DTRMWXHS-12 (DTRM-12), everolimus (EV) and pomalidomide (POM). This clinical trial met its primary endpoint. The once-daily oral triple combination therapy DTRM-555 has an acceptable safety profile. Encouraging clinical activity was observed in several high-risk, multi-refractory pts with RT (median 5 prior therapies, ORR 45%) or r/r DLBCL (median 2 prior therapies, ORR 60%), including pts previously treated with targeted therapies, cellular therapies, checkpoint inhibitors and other experimental agents."

Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Thrombocytopenia • Transplantation

Year in Review: Multiple Myeloma (MedPageToday) - "Dimopoulos noted that there are currently no approved agents for maintenance therapy in transplant-ineligible patients and options with a favorable toxicity profile are needed....At a median follow-up of 20.7 months, PFS had not been reached in the three-drug arm, as compared to 19.2 months in the control arm (HR 0.53, 99% CI 0.32-0.89, P=0.0007), reported Philippe Moreau, MD....'There was a signal of benefit and use of daratumumab as part of upfront treatment is strongly supported by this meta-analysis,' said Paul G. Richardson, MD...who was involved in some of the daratumumab trials included in the meta-analysis."

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Novel Treatment Approaches on the Horizon in Multiple Myeloma (THE ASCO POST) - "Kenneth C. Anderson, MD...shared his enthusiasm over these novel treatment approaches in a presentation during the 2020 Debates and Didactics in Hematology and Oncology Virtual Conference...'In the future, we will be able to achieve minimal residual disease negativity with our targeted therapies and restore host antimyeloma immunity with immunotherapy approaches,' Dr. Anderson said. 'When we do both, we will achieve long-term disease-free survival and potential cure.'"

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Safety Study of BTK Inhibitor, DTRMWXHS-12, Used Singly or in Combination, in CLL and B-cell Lymphomas (clinicaltrials.gov) - P1a/1b; N=48; Completed; Sponsor: Zhejiang DTRM Biopharma; Recruiting ➔ Completed

Clinical • Trial completion • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology