Author Interviews, Hematology / 19.12.2019

MedicalResearch.com Interview with: Tadeusz Robak MD, Ph.D. Professor of Hematology Medical University of Lodz, Poland MedicalResearch.com: What is the background for this study? What are the main findings?
  • Rozanolixizumab is an advanced SC anti-neonatal FcRn therapy currently in clinical development which has the potential to provide a targeted, convenient option to optimize individualized patient care.
  • The rozanolixizumab Phase II (TP0001) study was specifically designed to explore multiple dose regimens in order to inform the dosing strategy for further development in primary immune thrombocytopenia (ITP). Patients received either a single dose (1 x 15 mg/kg or 1 x 20 mg/kg) or multiple doses (5 x 4 mg/kg, 3 x 7 mg/kg, 2 x 10 mg/kg) of subcutaneous (SC) rozanolixizumab. The total dose was similar in all treatment groups, ranging from 15 to 21 mg/kg.
  • Rozanolixizumab was well tolerated by patients with primary ITP across all dose groups, consistent with previous rozanolixizumab studies. Additionally, improved platelet counts and reduced immunoglobin G (IgG) levels were seen at all doses and regimens of rozanolixizumab treatment, with higher response rate, higher percentage of responders and shorter time to response achieved by the 1 x 15 mg/kg, 1 x 20 mg/kg and the 3 x 7 mg/kg rozanolixizumab dose groups. These safety, tolerability and efficacy data support the Phase III development in patients with primary ITP.
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Author Interviews, Hematology, Lymphoma / 12.12.2019

MedicalResearch.com Interview with: Genentech Priscilla White, spokesperson Senior Manager, Corporate Relations Genentech MedicalResearch.com: What is the background for this study? What are the main findings?
  • Response: Mosunetuzumab is a T-cell engaging bispecific antibody designed to target CD20-positive B-cell blood cancers, by binding to both CD20 (on the surface of B-cells) and CD3 (on the surface of T-cells).
  • Analyses from the ongoing Phase I/Ib GO29781 study indicate that mosunetuzumab can produce durable responses in patients who have relapsed or who are refractory to prior treatment(s), including those who have relapsed or who are resistant to CAR T-cell therapy.
  • Results from this dose-escalation study showed encouraging efficacy with an objective response rate (ORR) of 62.7 percent (n=42/67) in slow-growing Non-Hodgkin Lymphoma and 37.1 percent (n=46/124) in aggressive NHL across all dose levels assessed.
  • Additionally, data demonstrated a complete response (CR) rate of 43.3 percent (n=29/67) in slow-growing NHL and 19.4 percent (n=24/124) in aggressive NHL. CRs showed durability, with 82.8 percent (n=24/29) of patients with slow-growing NHL remaining in remission up to 26 months off initial treatment and 70.8 percent (n=17/24) of patients with aggressive NHL, remaining in remission up to 16 months off initial treatment.
  • Of the participants who received prior CAR T-cell therapy, the ORR was 38.9 percent (n=7/18), and 22.2 percent (n=4/18) achieved a CR.
  • Adverse reactions included cytokine release syndrome (CRS) in 28.9 percent of patients with 20.0 percent at Grade 1 and 1.1 percent at Grade 3. Grade 3 neurological adverse events occurred in 3.7 percent of patients.
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Author Interviews, Cancer Research, Leukemia / 11.12.2019

MedicalResearch.com Interview with: Bridget Marcellino, MD Icahn School of Medicine at Mount Sinai Mount Sinai Hospital MedicalResearch.com: What is the background for this study? Response: Our work focuses on elucidating the mechanisms that drive the pathogenesis and progression of myeloproliferative neoplasms (MPN). Dysregulation of the TP53 pathway is associated with MPN progression evidenced by the association of TP53 loss of heterozygosity with transformation to acute myeloid leukemia (AML) and the presence of inactivating mutations of TP53 found in a proportion of MPN-related AML patients.   Studies have shown that TP53 mutations, TP53 deletions and overexpression of the negative regulator of TP53, Murine Double Minute 2 (MDM2) all contribute to TP53 downregulation in MPNs and we therefore are interested in exploring other potential means by which TP53 is downregulated. Protein Phosphatase, Mg2+/Mn2+ Dependent 1D (PPM1D) is another negative regulator of the TP53 pathway and activating mutations in this gene are present in myeloid malignancies including MPNS. We therefore hypothesized that genomic alterations in PPM1D and/or overexpression of PPM1D would be found in the hematopoietic cells of MPN patients. (more…)
Author Interviews, Hematology, Lymphoma / 10.12.2019

MedicalResearch.com Interview with: Steven M. Horwitz, MD Memorial Sloan Kettering Cancer Center New York, NY MedicalResearch.com: What is the background for this study? Response: Relapsed or refractory Peripheral T-Cell Lymphoma (R/R PTCL) remains a disease of significant unmet medical need. Duvelisib is an oral dual inhibitor of PI3K-δ and PI3K-γ approved for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies, relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies, and is being developed for the treatment of additional hematologic malignancies including R/R PTCL. In early studies, we saw a suggestion of quite good activity of duvelisib as a single agent in a range of subtypes of T-cell lymphoma. The PRIMO study is an ongoing, multi-center, open-label, registration-directed Phase 2 study evaluating duvelisib in patients with R/R PTCL that is expected to enroll approximately 120 patients. The study includes both a dose optimization phase and an expansion phase. The Primo study will be sufficiently powered to give a much more precise estimate of the activity in peripheral t cell lymphomas. However, prior to initiating the main cohort we needed to first try to identify an optimal dose. That “dose optimization cohort” is the subject of our presentation here. (more…)
Author Interviews, Hematology, Lymphoma / 10.12.2019

MedicalResearch.com Interview with: Prof. John Seymour, MBBS, Ph.D Lead investigator of the MURANO Trial Director. Department of Hematology at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia MedicalResearch.com: What is the background for this study? What are the main findings?
  • MURANO is an international, multicenter, open-label, randomized Phase 3 study designed to evaluate the efficacy and safety of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).
  • At this year’s American Society of Hematology (ASH) annual meeting, we presented results from the four-year updated analysis from the study, which showed an 81 percent reduction in the relative risk of disease progression or death in patients randomized to the chemotherapy-free, two year fixed-duration treatment course of venetoclax plus rituximab and higher rates of minimal residual disease (MRD)-negativity compared to the standard of care regimen, bendamustine plus rituximab.
  • The long-term data further support the sustained clinical benefit of fixed-duration treatment with venetoclax in combination with rituximab for this patient population.
  • The safety profile of the combination is consistent with the known safety profile of each individual therapy alone. There were no new serious safety issues observed in the MURANO study since the last update. 
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Author Interviews, Hematology, Lymphoma / 07.12.2019

MedicalResearch.com Interview with: Constantine Tam, M.D. Hematologist and Disease Group Lead Low Grade Lymphoma and CLL at Peter MacCallum Cancer Centre Victoria, Australia, and Lead study investigator of CAPTIVATE MedicalResearch.com: What is the background for this study? Response: The Phase 2 CAPTIVATE (PCYC-1142) clinical trial evaluated 164 patients younger than 70 years (median age of 58 years) with previously untreated CLL/SLL. Patients were planned to receive ibrutinib for 3 cycles, followed by 12 cycles of ibrutinib and venetoclax in combination. Ninety percent of patients was able to complete the planned therapy. MRD status was evaluated in PB after 6, 9, and 12 cycles and in BM after 12 cycles of the combination. (more…)
Author Interviews, Cancer Research, Lymphoma / 06.12.2019

MedicalResearch.com Interview with: Dr. Matthew S. Davids MD MSC Associate Director of the Dana-Farber CLL Center Attending physician Lymphoma Program, Division of Hematologic Malignancies Dana-Farber   Dr. Jennifer Crombie MD Instructor in Medicine Harvard Medical School    MedicalResearch.com: What is the background for this study? Response: New data from our investigator-sponsored Phase 1 study exploring duvelisib in combination with venetoclax will be presented at ASH on December 7. In relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), duvelisib plus venetoclax demonstrated promising clinical activity, a manageable tolerability profile, and identified a recommended Phase 2 dosing (RP2D) regimen.  (more…)