Tagged News
Bispecific Antibodies: Promising Advances Amid Adoption Challenges in Cancer Treatment
• Bispecific antibodies represent a significant advancement in cancer immunotherapy, targeting both tumor antigens and immune cells to enhance cytotoxicity without requiring patient-derived cells like CAR-T therapy.
• Despite clinical promise with nine FDA-approved bispecific antibodies, adoption faces challenges including transition between inpatient/outpatient settings, insurance coverage, adverse event management, and financial barriers in community settings.
• Recent approvals of Mosunetuzumab, Glofitamab, and Epcoritamab have shown impressive response rates in relapsed/refractory indolent B-cell lymphomas, with manageable toxicity profiles when using step-up dosing strategies.
Highlighted Clinical Trials:
Genmab
Posted 11/3/2020
Reid Merryman, MD
Posted 7/18/2023
University of Washington
Posted 3/23/2022
Abramson Cancer Center at Penn Medicine
Posted 11/5/2021
The Lymphoma Academic Research Organisation
Posted 9/5/2023
Hoffmann-La Roche
Posted 10/27/2021
NCT05529524Completed
The Lymphoma Academic Research Organisation
Posted 11/7/2022
Weill Medical College of Cornell University
Posted 11/1/2023
Clarity's 64Cu-SAR-bisPSMA Shows Promise in Detecting Prostate Cancer Recurrence in COBRA Trial
• Initial results from Clarity Pharmaceuticals' Phase 1/2 COBRA trial demonstrate that 64Cu-SAR-bisPSMA safely and effectively detects prostate cancer lesions in patients with biochemical recurrence who had negative standard-of-care imaging.
• The novel radiopharmaceutical identified lesions in up to 80% of patients on next-day imaging, with the number of detected lesions almost doubling compared to same-day imaging, highlighting a unique benefit of copper-64's longer half-life.
• Clinicians reported they would change treatment plans for approximately 50% of patients based on 64Cu-SAR-bisPSMA scan results, with two-thirds of these patients subsequently receiving focal or systemic therapy.
Highlighted Clinical Trials:
Clarity Pharmaceuticals Ltd
Posted 4/11/2022
Clarity Pharmaceuticals Ltd
Posted 12/21/2023
Clarity Pharmaceuticals Ltd
Posted 7/13/2021
Merck and Daiichi Sankyo Form $22 Billion Alliance for Three Novel Antibody-Drug Conjugates
• Merck will pay Daiichi Sankyo $4 billion upfront plus $1.5 billion in continuation payments, with potential additional milestone payments reaching a total of $22 billion.
• The collaboration focuses on three investigational antibody-drug conjugates: patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd), and raludotatug deruxtecan (R-DXd), targeting multiple solid tumors.
• Patritumab deruxtecan has received Breakthrough Therapy Designation for EGFR-mutated non-small cell lung cancer, with a biologics license application planned by March 2024.
Highlighted Clinical Trials:
Daiichi Sankyo
Posted 3/9/2022
Daiichi Sankyo
Posted 2/2/2021
Daiichi Sankyo
Posted 12/22/2020
Novel Targets and Strategic Sequencing: The Evolving Landscape of T-Cell Redirection Therapies in Multiple Myeloma
• CAR T-cell therapies and bispecific antibodies targeting BCMA and GPRC5D are transforming multiple myeloma treatment, with ciltacabtagene autoleucel showing unprecedented efficacy with a median PFS of 34.9 months in heavily pretreated patients.
• Disease progression rate is a critical factor in therapy selection, with rapidly progressing patients better suited for "off-the-shelf" bispecific antibodies, while patients with indolent disease may benefit more from CAR T-cell therapies despite longer manufacturing times.
• Strategic sequencing of therapies is crucial, as prior BCMA-directed bispecific antibody treatment significantly reduces the efficacy of subsequent BCMA-targeted CAR T-cell therapy, highlighting the importance of preserving T-cell fitness and considering antigen loss.
Highlighted Clinical Trials:
Janssen Research & Development, LLC
Posted 6/12/2020
Pfizer
Posted 2/2/2021
Janssen Research & Development, LLC
Posted 9/17/2020
Celgene
Posted 4/16/2019
Celgene
Posted 12/13/2017
Janssen Research & Development, LLC
Posted 11/7/2019
Janssen Research & Development, LLC
Posted 2/1/2021
Janssen Research & Development, LLC
Posted 6/29/2018
Samuraciclib Shows Promise in Advanced Breast Cancer Patients After CDK4/6 Inhibitor Failure
• Phase I clinical trials demonstrate samuraciclib, a selective CDK7 inhibitor, has an acceptable safety profile with manageable gastrointestinal side effects and shows clinical activity in various advanced solid tumors.
• In HR+/HER2- breast cancer patients who progressed on CDK4/6 inhibitors, the combination of samuraciclib with fulvestrant achieved a clinical benefit rate of 36% and median progression-free survival of 3.7 months.
• Exploratory analysis revealed patients without TP53 mutations had significantly longer progression-free survival (7.4 months vs 1.8 months), suggesting TP53 status may serve as a potential biomarker for treatment response.
Highlighted Clinical Trials:
Carrick Therapeutics Limited
Posted 11/14/2017
Revumenib Shows Promise in Phase 1 Trial for KMT2A-Rearranged and NPM1-Mutated Acute Leukemia
• Revumenib, a first-in-class menin inhibitor, demonstrated a 30% complete remission rate in heavily pretreated patients with KMT2A-rearranged or NPM1-mutated acute leukemia, with 78% achieving undetectable measurable residual disease.
• The oral therapy works by disrupting the menin-KMT2A interaction, downregulating key leukemogenic genes and promoting differentiation of leukemic cells, addressing a critical unmet need for these poor-prognosis genetic subtypes.
• While QT interval prolongation was the most common treatment-related adverse event (53%), the phase 1 trial established recommended phase 2 dosing with manageable safety profile, supporting further development of this targeted therapy.
BriaCell Advances Pivotal Study for Bria-IMT in Metastatic Breast Cancer Following Positive FDA Feedback
• BriaCell Therapeutics has received positive FDA feedback for its pivotal study of Bria-IMT in combination with a checkpoint inhibitor for advanced metastatic breast cancer, potentially accelerating commercialization.
• The FDA has agreed on the eligible patient population—breast cancer patients who have failed available approved therapies—and the primary endpoint of survival improvement compared to physician's choice of treatment.
• BriaCell is also preparing to launch its Bria-OTS personalized treatment program, which matches patients' HLA type with pre-manufactured cells, with dosing expected to begin in the first half of 2023.
Cullinan Oncology and Taiho Pharmaceutical Forge $275M Strategic Collaboration for EGFR Inhibitor CLN-081/TAS6417
• Taiho Pharmaceutical will acquire Cullinan Pearl for $275 million upfront plus up to $130 million in regulatory milestones, gaining exclusive global rights to CLN-081/TAS6417 outside the U.S.
• CLN-081/TAS6417 is an oral, irreversible EGFR inhibitor targeting exon 20 insertion mutations in non-small cell lung cancer, which affect approximately 2-3% of NSCLC patients globally.
• The companies will jointly develop and co-commercialize the drug in the U.S. with equal profit sharing, while Taiho will commercialize in territories outside the U.S. and China.
Zanidatamab Plus Chemotherapy Shows Promising Results in Heavily Pretreated HER2-Positive Breast Cancer
• Zanidatamab, a novel HER2-targeted bispecific antibody, demonstrated a 36.4% objective response rate and 86.4% disease control rate when combined with chemotherapy in heavily pretreated HER2-positive breast cancer patients.
• The combination therapy showed a median progression-free survival of 7.3 months, with 42% of patients still on treatment at data cutoff, offering new hope for patients who have progressed after multiple HER2-targeted therapies.
• The treatment was well-tolerated with manageable side effects, primarily low-grade diarrhea, supporting further investigation as a potential new therapeutic option for advanced HER2-positive breast cancer.
Highlighted Clinical Trials:
Jazz Pharmaceuticals
Posted 9/30/2016
Lorlatinib Shows Promising Efficacy in ALK-Rearranged NSCLC with 21.8 Month Median PFS
• A real-world study of lorlatinib in ALK-rearranged non-small cell lung cancer demonstrated a median progression-free survival of 21.8 months, significantly higher than in previous trials.
• The objective response rate was 43% with disease control achieved in 94% of patients, while 81% of patients with brain metastases showed objective response for intracranial lesions.
• Patients experiencing adverse events, particularly hypercholesterolemia and edema, had significantly better outcomes than those without side effects, suggesting a potential correlation between drug exposure and efficacy.