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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.

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.

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

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

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

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

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

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

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

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

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.

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

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

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.

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

Phase I Trial of Defactinib and VS-6766.

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

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

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

Revumenib Shows Breakthrough Results in Advanced Acute Myeloid Leukemia Trial

Targeted Therapy
  • Revumenib, a novel menin inhibitor, achieved complete remission in 30% of heavily pretreated acute myeloid leukemia patients in the phase 1 AUGMENT-101 trial.
  • The drug works by disrupting the menin-MLL1 protein complex, reprogramming leukemia cells back into normal blood cells or causing them to die.
  • Twelve patients who achieved remission successfully underwent stem cell transplants, with nine remaining in remission at last analysis.
  • The treatment targets specific genetic alterations (KMT2A rearrangements and NPM1 mutations) found in 30-40% of AML cases, potentially benefiting up to 50% of all acute myeloid leukemias.

Revumenib Shows Promise in Phase 1 Trial for KMT2A-Rearranged and NPM1-Mutated Acute Leukemia

OncologyTargeted Therapy
  • 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.
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