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NIH's Novel Five-Drug Combination Shows Promise for Relapsed Aggressive B-Cell Lymphoma

Targeted TherapyOncologyMonoclonal Antibody
  • NIH researchers have developed ViPOR, a non-chemotherapy five-drug regimen that achieved complete remission in 38% of patients with relapsed or refractory diffuse large B-cell lymphoma.
  • The treatment was particularly effective in two specific subtypes: non-GCB DLBCL (62% complete response) and double-hit GCB DLBCL (53% complete response), offering new hope for patients with limited options.
  • At the two-year mark, 36% of all treated patients were still alive and 34% remained disease-free, with some maintaining remission beyond four years despite previously facing poor prognoses.

New Trial Data Shows Enhertu Reduces Breast Cancer Progression Risk by 38% as Access Remains Denied in England

Targeted TherapyOncology
  • New trial results from the Destiny-Breast06 study show Enhertu reduced the risk of HER2-low breast cancer progression by 38% compared to standard chemotherapy, with patients living without disease progression for 13.2 months versus 8.1 months.
  • The drug demonstrated superior efficacy with 60% of patients responding to treatment compared to 30% with chemotherapy, building on previous studies showing overall survival improvements of over six months.
  • Despite compelling clinical evidence, approximately 1,000 women annually in England and Wales are denied access to Enhertu due to NICE's cost-effectiveness concerns, while the drug remains available in Scotland and 13 other European countries.
  • Patient advocates and charities describe the access disparity as "utterly unacceptable," with ongoing negotiations between NICE, NHS England, and manufacturers Daiichi Sankyo and AstraZeneca to resolve pricing issues.

FDA Grants Accelerated Approval to Krazati Plus Cetuximab for KRAS G12C-Mutated Colorectal Cancer

Drug ApprovalPrecision MedicineTargeted Therapy
  • The FDA granted accelerated approval to Krazati (adagrasib) plus cetuximab for adults with KRAS G12C-mutated locally advanced or metastatic colorectal cancer who have received prior standard chemotherapy treatments.
  • The combination therapy targets a specific genetic mutation and is approved for patients whose tumors are determined to have the KRAS G12C mutation by an FDA-approved test.
  • The most common adverse reactions include rash, nausea, diarrhea, vomiting, fatigue, and musculoskeletal pain, occurring in at least 20% of patients.
  • This approval represents a significant advancement in precision medicine for colorectal cancer patients with this specific genetic alteration.

Combination Immunotherapy Strategies Show Promise in Overcoming NSCLC Treatment Resistance

Targeted Therapy
  • Combination immunotherapies demonstrate superior efficacy compared to monotherapy approaches in NSCLC, with dual checkpoint inhibition and chemo-immunotherapy combinations showing improved overall survival and progression-free survival rates.
  • Multiple resistance mechanisms to targeted therapies and immunotherapy have been identified in NSCLC, including target-dependent mutations, bypass pathway activation, and tumor microenvironment changes that limit treatment effectiveness.
  • Novel therapeutic strategies including fourth-generation EGFR-TKIs, antibody-drug conjugates, and combination approaches targeting multiple pathways are being developed to overcome resistance mechanisms.
  • Biomarker-driven patient selection and personalized treatment approaches are emerging as critical factors for optimizing combination therapy outcomes in NSCLC patients.

Merck Launches Phase 3 Trial of MK-1084 Plus Pembrolizumab for KRAS G12C-Mutated NSCLC

Targeted Therapy
  • Merck has initiated a phase 3 trial evaluating MK-1084, an investigational oral KRAS G12C inhibitor, in combination with pembrolizumab as first-line treatment for metastatic NSCLC patients with KRAS G12C mutations and PD-L1 expression ≥50%.
  • The double-blind, multicenter trial will enroll approximately 600 patients globally, with primary endpoints of progression-free survival and overall survival.
  • Phase 1 data showed promising efficacy with a 47% overall response rate for the combination therapy compared to 19% for MK-1084 monotherapy.
  • KRAS G12C is the most common KRAS mutation in NSCLC patients, occurring in approximately 14% of adenocarcinomas, representing a significant unmet medical need.

Sacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004)

NCT06074588RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 11/12/2023

A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)

NCT05067283RecruitingPhase 1
Merck Sharp & Dohme LLC
Posted 12/17/2021

Sacituzumab Tirumotecan (MK-2870) in Post Platinum and Post Immunotherapy Endometrial Cancer (MK-2870-005)

NCT06132958RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 12/6/2023

A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006)

NCT06079879RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 12/31/2023

A Study of MK-1084 Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004/KANDLELIT-004)

NCT06345729RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 5/24/2024

A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/BELLWAVE-011)

NCT06136559RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 12/13/2023

Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)

NCT06136624Active, Not RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 12/31/2023

A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)

NCT06136650RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 12/18/2023

A Study of Nemtabrutinib vs Chemoimmunotherapy for Participants With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without TP53 Aberrations (MK-1026-008, BELLWAVE-008)

NCT05624554Active, Not RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 3/16/2023

Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% (MK-2870-007)

NCT06170788RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 12/15/2023

Ascentage Pharma's Lisaftoclax Receives FDA Clearance for Global Phase III Trial in CLL/SLL

Targeted Therapy
  • Ascentage Pharma received FDA clearance to proceed with a global registrational Phase III clinical trial for lisaftoclax (APG-2575) in previously BTKi-treated CLL/SLL patients.
  • The novel Bcl-2 inhibitor demonstrated promising efficacy in earlier studies, with ORRs of 100% in treatment-naïve patients and 98% in relapsed/refractory patients when combined with acalabrutinib.
  • Lisaftoclax could potentially become the second Bcl-2 inhibitor approved globally, addressing significant unmet medical needs in CLL/SLL treatment.
  • Clinical data from three studies were presented at ASH 2023, showing efficacy across multiple hematologic malignancies including AML and multiple myeloma.

Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL

NCT04494503RecruitingPhase 1
Ascentage Pharma Group Inc.
Posted 8/31/2020

A Study to Evaluate the Safety,PK and PD of APG-2575 in Patients With Hematologic Malignancies

NCT03913949Active, Not RecruitingPhase 1
Ascentage Pharma Group Inc.
Posted 6/3/2019

Merck and Daiichi Sankyo Form $22 Billion Alliance for Three Novel Antibody-Drug Conjugates

OncologyTargeted TherapyPrecision Medicine
• 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.

Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

NCT05280470Active, Not RecruitingPhase 2
Daiichi Sankyo
Posted 3/9/2022

A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors

NCT04707248Active, Not RecruitingPhase 1
Daiichi Sankyo
Posted 12/22/2020

HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer

NCT04619004Active, Not RecruitingPhase 2
Daiichi Sankyo
Posted 2/2/2021

Samuraciclib Shows Promise in Advanced Breast Cancer Patients After CDK4/6 Inhibitor Failure

OncologyTargeted TherapyPrecision Medicine
  • 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.

Modular Study to Evaluate CT7001 Alone in Cancer Patients With Advanced Malignancies

NCT03363893CompletedPhase 1
Carrick Therapeutics Limited
Posted 11/14/2017

Tango Therapeutics Initiates Phase 1/2 Trial of TNG462 for MTAP-Deleted Solid Tumors

Targeted Therapy
  • Tango Therapeutics has dosed the first patient in a phase 1/2 clinical trial of TNG462, a potentially best-in-class MTA-cooperative PRMT5 inhibitor targeting MTAP-deleted solid tumors.
  • MTAP deletions occur in 10-15 percent of solid tumors and currently have no FDA-approved treatments specifically designed for this genetic alteration.
  • TNG462 selectively targets cancer cells with MTAP deletion while sparing normal cells, and demonstrated deep tumor regressions in preclinical models across multiple cancer types.
  • The company is also advancing TNG908, a brain-penetrant PRMT5 inhibitor, in a separate ongoing phase 1/2 study to address a broader range of indications.

Avutometinib-Defactinib Combination Shows 45% Response Rate in Low-Grade Serous Ovarian Cancer

Targeted TherapyOncology
  • A phase II trial of avutometinib combined with defactinib demonstrated a 45% response rate in patients with advanced low-grade serous ovarian cancer, nearly twice as effective as current best treatments.
  • Patients with KRAS mutations showed particularly strong responses at 60%, while those without mutations still achieved a 29% response rate, both significantly higher than standard therapy response rates of 0-14%.
  • The dual RAF/MEK inhibitor combination proved over four times more effective than avutometinib alone, with previous phase I data showing an average progression-free survival of 23 months.
  • Low-grade serous ovarian cancer affects approximately 700 women annually in the UK and represents about 10% of all ovarian cancer cases, typically affecting younger women with poor response to conventional treatments.

Phase I Trial of Defactinib and VS-6766.

NCT03875820Active, Not RecruitingPhase 1
Institute of Cancer Research, United Kingdom
Posted 12/12/2017

Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

NCT02101788Active, Not RecruitingPhase 2
National Cancer Institute (NCI)
Posted 2/27/2014

A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer

NCT01849874TerminatedPhase 3
Pfizer
Posted 6/27/2013

A Study of Avutometinib (VS-6766) V. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer with and Without a KRAS Mutation

NCT04625270Active, Not RecruitingPhase 2
Verastem, Inc.
Posted 12/21/2020

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