Encouraging ORR Observed With CLR 131 as CLOVER-1 Heads To Pivotal Stage – Targeted Oncology
By daniellenierenberg
CLR 131, a phospholipid ether molecule, is showing promising disease control in an ongoing phase 2 study (CLOVER-1, NCT02952508) as treatment of patients with relapsed or refractory lymphoplasmacytic lymphoma (LPL) and Waldenstrm macroglobulinemia (WM), according to initial study results.
The findings were presented in a poster during the American Association for Cancer Research (AACR) Virtual Meeting: Advances in Malignant Lymphoma by Jarrod Longcor, chief business officer of Cellectar Biosciences, Inc, the developer of CLR 131.
Prior to the initiation of the phase 2 study, the potential of CLR 131 was demonstrated throughin vitro, in vivo, and preclinical studies. The agent works by binding to and entering the tumor via lipid rafts, which stabilize tumor cells. This mechanism of action is particularly effective in hematologic malignancies.
Read earlier data on CLR 131 here.
Four patients with LPL/WM were enrolled to assess interim efficacy and safety in part A of the trial. The median age of the population was 70 years (range, 54-81). Three of the patients had an ECOG performance status of 0. The mean prior number of therapies received was 2.5 with a median of 2 (range, 1-5). All patients had received prior rituximab (Rituxan); ibrutinib (Imbruvica) and autologous stem cell transplant were received by 1 patient each. In addition, 75% of patients received other agents.
Efficacy in the Overall Population
The objective response rate (ORR) observed with CLR 131 in the LPL/WM population treated in part A of CLOVER-1 was 100% with a major response to treatment observed in 3 patients after 2 to 4 doses of the drug. Despite the characteristics of these heavily pretreated patients, CLR 131 is the only monotherapy that has achieved responses in the relapsed or refractory population.
In the overall population of 4 patients, survival and duration of response (DOR) were also assessed. Two patients in the study received 1 cycle of CLR 131 (2 doses total) and the other 2 received 2 cycles (4 doses total).
Of the 2 patients receiving 1 cycles of therapy, patient 1 had an overall survival (OS) duration 16.4 month, a progression-free survival (PFS) of 16.4 months, and a DOR of 15 months. The same patient had a major response to therapy. The second patients had an OS and PFS of 13.8 months and a DOR of 13.1 months. The response observed in this patient was a partial response (PR).
Of the 2 patients receiving 2 cycles of therapy, patient 3 had the longest OS and PFS at 33.2 with a DOR of 31.7 months and a complete response to treatment. Finally, patient 4 had an OS and PFS of 10.1 months with a DOR of 8.4 months. The type of response shown with patient 4 was a PR.
In all patients, the median DOR was not reached and the ongoing mean was calculated as 17.1 months. Evaluation of all patient responses is ongoing.
Longer-Term Response in Elderly Patient
One patient in the study was a 66-year-old female who, at baseline, presented with pleural effusion and 5 large extra-medullary nodules in the third-line setting. She was refractory to all of the prior treatment she received. CLR 131 in this patient, however, led to 100% overall tumor burden reduction as well as complete resolution of all tumors. The tumor locations resolved included a subdiaphragmatic mass, left epicardial mass, aortic bifurcation, right ovary, and left ovary. This result occurred by day 187. In terms of the duration of complete response, CT and bone marrow biopsy performed at day 406 revealed the patient had a duration of response of over 31 months.
Safety in the Overall Population
The safety analysis in all patients with non-Hodgkin lymphoma treated on the trial (n = 19) revealed treatment-emergent adverse events (TEAEs) that occurred in 15% or more included thrombocytopenia (83%), lymphocyte count decreased (25%), decreased white blood cell count (58%), anemia (58%), and neutropenia (50%). In the LPL population alone, the most common events observed were neutropenia (100%), thrombocytopenia (100%), and fatigue (75%). The analysis demonstrated that patients with extramedullary disease have lower rates of cytopenias at lower grades. The drug was overall well-tolerated in patients.
CLOVER-1 is an open-label, multicenter, 2-part study. In part A, which is now completed, patients with multiple myeloma, diffuse large B-cell lymphoma, LPL/WM, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic leukemia, and marginal zone lymphoma were assessed for interim CLR 131 efficacy. Patients in part A received a starting dose of less than 50 mCi total body dose of CLR131, following by 50 mCi then 75 mCi. Part B is actively enrolling patients with multiple myeloma and LPL/WM to assess the clinical benefit rate, ORR, time to response, time to progression, and OS. Patients in part B will receive either 1 or 2 cycles of CLR 131 100 mCi total body dose.
Read more about CLR 131 for the treatment of hematologic malignancies.
Reference
Ailwadhi S, Longcor, J Oliver K, and Grachev I. CLR 131 demonstrates 100% overall response rate in relapsed or refractory lymphoplasmacytic lymphoma (LPL)/Waldenstroms macroglobulinemia (WM): initial results from ongoing phase 2 trial, CLOVER-1 study. Presented at: American Association for Cancer Research Virtual Meeting: Advances in Malignant Lymphoma; Aug 1719, 2020. Abstract PO-25
Continued here:
Encouraging ORR Observed With CLR 131 as CLOVER-1 Heads To Pivotal Stage - Targeted Oncology
- Rejuvenating the immune system by depleting certain stem cells - National Institutes of Health (NIH) (.gov) - April 19th, 2024
- New gene therapy eliminates need for bone marrow transplant. Here's how it works. - CBS News - April 19th, 2024
- New gene therapy eliminates need for bone marrow transplant. Here's how it works. - MSN - April 19th, 2024
- Long Island boy with rare blood disorder undergoes gene therapy - MSN - April 19th, 2024
- Philadelphia Wings player, Connecticut man will be forever bonded by bone marrow donation: "He's my hero" - CBS Philly - April 10th, 2024
- VRD versus VCD as induction therapy before autologous stem cell transplantation in multiple myeloma: a nationwide ... - Nature.com - April 10th, 2024
- Register as a bone marrow donor today and save lives - The Citizen - April 10th, 2024
- Resilient anatomy and local plasticity of naive and stress haematopoiesis - Nature.com - March 26th, 2024
- A Deeper Depth of Response After Salvage Therapy Improves Outcomes of Autologous Stem Cell Transplantation in ... - Cureus - March 26th, 2024
- Iron restriction keeps blood stem cells young, researchers find - Phys.org - March 18th, 2024
- Blood drive, bone marrow testing to be held in local woman's memory - The Winchester Star - March 18th, 2024
- Signal of Benefit for Stem Cell Therapy in Progressive MS - Medscape - March 10th, 2024
- Woman, 22, With Leukemia Recalls Symptoms And New Treatment She Received: EXCLUSIVE - TODAY - March 10th, 2024
- This Swedish startup wants to reduce the cost, and controversy, around stem cell production - TechCrunch - March 10th, 2024
- Outcomes and prognosis of haploidentical haematopoietic stem cell transplantation in children with FLT3-ITD mutated ... - Nature.com - March 10th, 2024
- Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor ... - Nature.com - March 10th, 2024
- Hematopoietic cell transplantation and cell therapy activity landscape survey in the Kingdom of Saudi Arabia; a report ... - Nature.com - March 10th, 2024
- How an MS friendship led to HSCT and a love of running - Multiple Sclerosis News Today - March 10th, 2024
- Iron Limitation Preserves Youthfulness of Blood Stem Cells - Mirage News - March 10th, 2024
- Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the ... - Nature.com - March 10th, 2024
- AJMC in the Press, February 23, 2024 - AJMC.com Managed Markets Network - February 24th, 2024
- Orca Bio Presents Promising Data on Orca-T in Two Oral Presentations at the 2024 Tandem Meetings of ASTCT and ... - Yahoo Finance - February 24th, 2024
- New approaches to live-track the production of different types of blood cells in mice - Medical Xpress - February 24th, 2024
- If Other Treatments Aren't Working -- Stem Cell Transplant May Be A Good Option In CLL - SurvivorNet - February 24th, 2024
- Expanding the Horizons of Cell and Gene Therapy - RegMedNet - February 24th, 2024
- The strangers who saved each others lives - BBC - February 24th, 2024
- City of Hope Research Featuring the Successful Treatment of the Oldest Patient to Achieve Remission for Leukemia ... - StreetInsider.com - February 15th, 2024
- 3D printing and material processing combined to create artificial bone - Optics.org - February 15th, 2024
- Man, 63, is in remission from HIV five years after receiving groundbreaking stem cell transplant... - The Sun - February 15th, 2024
- Team demonstrates fabrication method to construct 3D structures that mimic bone microstructure - Phys.org - February 15th, 2024
- Hematopoietic Stem Cells and Their Role in Development and Disease Therapy - The Scientist - February 15th, 2024
- Blood cell family trees trace how production changes with aging - MIT News - February 7th, 2024
- New study on promising stem cell-based therapy for Crohn's disease - Medical Xpress - January 30th, 2024
- Second haploidentical bone marrow transplantation with antithymocyte antibody-containing conditioning regimen for ... - Nature.com - January 30th, 2024
- Stem cell study shows how gene activity modulates the amount of immune cell production in mice - Medical Xpress - January 30th, 2024
- Global Stem Cell Therapy Industry Outlook to 2028, Driven by Therapeutic Innovations and Clinical Advancements ... - Yahoo Finance - January 30th, 2024
- 1st-of-its-kind therapy blocks immune attack after stem-cell transplant - Livescience.com - January 22nd, 2024
- Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric ... - Nature.com - January 22nd, 2024
- Implications of stress-induced gene expression for hematopoietic stem cell aging studies - Nature.com - January 22nd, 2024
- LVHN announces opening of new stem cell transplant center. Here's what that means for the Lehigh Valley - The Morning Call - January 22nd, 2024
- Fast Five Quiz: Chronic GVHD Risk Factors and Prevention - Medscape Reference - January 22nd, 2024
- Could Treatments for HIV and Sickle Cell Open the Gene Therapy Floodgates? - BioSpace - January 22nd, 2024
- Effects of fine particulate matter on bone marrow-conserved hematopoietic and mesenchymal stem cells: a systematic ... - Nature.com - January 14th, 2024
- Donating Bone Marrow and Stem Cells: The Process and What To Expect - On Cancer - Memorial Sloan Kettering - January 14th, 2024
- No, Rep. Steve Scalise Didn't Vote Against Stem Cell Research From Which He Is Now Benefiting - Yahoo News - January 14th, 2024
- Hematopoietic Stem Cell Transplantation Market to Grow Rapidly During the Study Period (2019-2032), Evaluates ... - PR Newswire - January 14th, 2024
- Life-saving donation from Philly athlete saves life: 'Feeling so strong, I owe that all to him' - AOL - January 14th, 2024
- The Key to Creating Blood Stem Cells May Lie in Your Own Blood - ScienceAlert - January 14th, 2024
- Dr Phillips on the Rationale for the GLOBRYTE Trial in Relapsed/Refractory MCL - OncLive - January 14th, 2024
- COVID-19 and HSCT Recipients: Risk Factors and Prevention Measures - Medriva - January 14th, 2024
- Bone Marrow Transplant: Heres What You Need To Know About This Therapy - Times Now - January 5th, 2024
- New insights about the development of hematopoietic stem cells - Drug Target Review - December 28th, 2023
- Bone Marrow Transplantation | Johns Hopkins Medicine - December 20th, 2023
- Stem Cell or Bone Marrow Transplant | American Cancer Society - December 20th, 2023
- Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental contact urticaria by regulating the functions ... - Nature.com - December 20th, 2023
- Researchers discover crucial step in creating blood stem cells - Phys.org - December 20th, 2023
- A niche topic: understanding the development of hematopoietic stem cells - Fred Hutchinson Cancer Center - December 20th, 2023
- Vertex developed a CRISPR cure. Its already on the hunt for something better. - MIT Technology Review - December 20th, 2023
- FDA approves cure for sickle cell disease, the first treatment to use gene-editing tool CRISPR - NBC News - December 12th, 2023
- First therapy using CRISPR technology will treat sickle cell disease - Morning Brew - December 12th, 2023
- 7 medical breakthroughs that gave us hope in 2023 - National Geographic - December 12th, 2023
- Understanding Chronic Myeloid Leukemia: Causes, Symptoms, and Treatment - Everyday Health - December 12th, 2023
- Mansour bin Zayed witnesses inauguration of ADSCC Bone Marrow Transplant & Cellular Therapy Congress 2023 - ZAWYA - November 26th, 2023
- ADSCC Bone Marrow Transplant and Cellular Therapy Congress 2023 to take place in Abu Dhabi - ZAWYA - November 18th, 2023
- Orchard Therapeutics Reports First Quarter 2023 Financial Results and Announces Initiation of Rolling Submission for Biologics License Application of... - May 16th, 2023
- Family of 7-month-old in need of bone marrow transplant hosting donor registration event - CBS Pittsburgh - May 8th, 2023
- Anika Continues to Expand Addressable Market for Tactoset Injectable Bone Substitute with Additional 510(k) Clearance from FDA - Marketscreener.com - April 5th, 2023
- MorphoSys Completes Enrollment of Phase 3 MANIFEST-2 Study of Pelabresib in Myelofibrosis with Topline Results Expected by End of 2023 -... - April 5th, 2023
- VOR BIOPHARMA INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-K) - Marketscreener.com - March 25th, 2023
- BioRestorative Therapies to Seek FDA Approval to Expand the Clinical Application of BRTX-100 - Marketscreener.com - March 17th, 2023
- BioSenic delivers a new post-hoc analysis of its Phase III JTA-004 trial on knee osteo-arthritis with positive action on the most severely affected... - March 17th, 2023
- JASPER THERAPEUTICS, INC. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - March 9th, 2023
- For a range of unmet medical needs, India offers a fantastic opportunity to push cell and gene therapies: B .. - ETHealthWorld - March 9th, 2023
- NGM BIOPHARMACEUTICALS INC Management's Discussion and Analysis of Financial Condition and Results of Operations. (form 10-K) - Marketscreener.com - March 1st, 2023
- Bone health: Tips to keep your bones healthy - Mayo Clinic - January 27th, 2023
- Bone marrow drive held for military wife with cancer - January 27th, 2023
- Bone cancer - Symptoms and causes - Mayo Clinic - January 27th, 2023
- Bone | Definition, Anatomy, & Composition | Britannica - January 19th, 2023
- Bone Definition & Meaning - Merriam-Webster - January 19th, 2023
- What Is Bone? | NIH Osteoporosis and Related Bone Diseases National ... - January 19th, 2023