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Clinical Trial News

Dato-DXd Plus Durvalumab Shows Variable pCR Rates in High-Risk Breast Cancer Subtypes

• The I-SPY 2.2 trial evaluated datopotamab deruxtecan (Dato-DXd) plus durvalumab in stage II/III high-risk HER2-negative breast cancer, revealing an overall pathologic complete response (pCR) rate of 50%. • Treatment response varied significantly across response predictive subtypes (RPS), with the HR-negative/HER2-negative/immune-negative/DRD-negative subtype showing a pCR rate of 44% compared to 16% in the control. • The combination's toxicity profile was consistent with prior studies, and a substantial proportion of pCRs were achieved early in treatment, potentially avoiding standard chemotherapy. • These findings support further investigation in randomized controlled trials, particularly focusing on immune-positive and HR-negative/DRD-negative subtypes to optimize neoadjuvant breast cancer treatment.

I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer

NCT01042379RecruitingPhase 2
QuantumLeap Healthcare Collaborative
Posted 3/1/2010

A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer

NCT03742102Active, Not RecruitingPhase 1
AstraZeneca
Posted 12/21/2018

ESMO 2024: Optimizing Post-IO Therapy in Clear Cell and Expanding Options for Non-Clear Cell RCC

• The TiNivo-2 trial found that tivozanib plus nivolumab was not superior to tivozanib alone in patients with renal cell carcinoma (RCC) following prior immune checkpoint inhibitor therapy. • The LITESPARK-005 study demonstrated that belzutifan maintains a progression-free survival benefit versus everolimus in previously treated advanced clear cell RCC, but is not a new benchmark. • The SUNNIFORECAST trial showed encouraging overall survival and objective response rates with nivolumab plus ipilimumab versus standard of care in non-clear cell RCC, though heterogeneity exists.

KarXT Approval Faces Scrutiny Over Potential Labeling Issues, Analyst Warns

  • Bristol-Myers Squibb's KarXT, aimed at treating schizophrenia, faces potential FDA approval hurdles due to labeling concerns regarding cardiovascular risks and food effects.
  • An analyst from Morgan Stanley maintains a Sell rating on BMY stock, anticipating a negative market reaction if KarXT's label includes restrictive cardiovascular monitoring measures.
  • Investor expectations lean towards a positive outcome with a clean label, which would likely result in a modest increase in BMY’s stock value, but labeling issues could hinder market performance.
  • Substantial growth in BMY's stock from KarXT would likely require significant contribution from the Alzheimer’s disease psychosis indication or failure of ABBV’s emraclidine.

T-DXd Combinations Show Promise in HER2+ Gastric and GEJ Cancers

• Trastuzumab deruxtecan (T-DXd) combined with fluoropyrimidine showed notable antitumor activity in HER2-positive gastric and gastroesophageal junction (GEJ) cancers. • The combination of T-DXd and fluoropyrimidine yielded the highest overall response rate (ORR) of 78% and a median progression-free survival (PFS) of 20 months. • Adding pembrolizumab to T-DXd and fluoropyrimidine introduced greater toxicities, including a higher incidence of drug-related interstitial lung disease. • A reduced-dose triplet of T-DXd, fluoropyrimidine, and pembrolizumab showed manageable safety, warranting further investigation in HER2-positive tumors.

Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)

NCT04379596RecruitingPhase 2
AstraZeneca
Posted 6/3/2020

Enfortumab Vedotin Plus Pembrolizumab Shows Durable Response in Advanced Urothelial Carcinoma

  • Five-year follow-up data from EV-103 study shows enfortumab vedotin plus pembrolizumab yields durable responses in cisplatin-ineligible, advanced urothelial carcinoma patients.
  • The combination therapy achieved a 73.3% overall response rate, with 41.5% of patients alive at five years, surpassing historical benchmarks.
  • The median overall survival reached 26 months, supporting the use of enfortumab vedotin plus pembrolizumab as a first-line standard of care.
  • Treatment-related adverse events, such as skin reactions and peripheral neuropathy, were manageable, with most resolving or improving after discontinuation.

A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer

NCT03288545Active, Not RecruitingPhase 1
Astellas Pharma Global Development, Inc.
Posted 10/11/2017

Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

NCT04223856Active, Not RecruitingPhase 3
Astellas Pharma Global Development, Inc.
Posted 3/30/2020

iTeos' TIGIT Inhibitor Shows Promise in Lung Cancer, Reviving Interest in the Target

• iTeos Therapeutics' belrestotug, combined with GSK's Jemperli, demonstrated encouraging tumor shrinkage in lung cancer patients, with overall response rates significantly higher than Jemperli alone. • The Phase 2 trial results have sparked renewed interest in TIGIT as a therapeutic target, despite previous setbacks with other TIGIT inhibitors from companies like Roche and Merck. • Safety concerns exist, as the combination therapy was associated with a higher incidence of serious side effects and treatment-related deaths compared to Jemperli monotherapy. • iTeos and GSK have initiated a Phase 3 trial to further evaluate the efficacy and safety of belrestotug plus Jemperli against the current standard of care, Keytruda.

Study of Pembrolizumab/Vibostolimab (MK-7684A) in Combination With Concurrent Chemoradiotherapy Followed by Pembrolizumab/Vibostolimab Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Stage III Non-small Cell Lung Cancer (MK-7684A-006)

NCT05298423Active, Not RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 5/3/2022

Coformulation of Pembrolizumab/Vibostolimab (MK-7684A) Versus Pembrolizumab (MK-3475) Monotherapy for Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Metastatic Non-Small Cell Lung Cancer (MK-7684A-003, KEYVIBE-003)

NCT04738487Active, Not RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 4/7/2021

Study of Pembrolizumab/Vibostolimab Coformulation (MK-7684A) in Combination With Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (MK-7684A-007/KEYVIBE-007)

NCT05226598Active, Not RecruitingPhase 3
Merck Sharp & Dohme LLC
Posted 3/24/2022

A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)

NCT06472076Active, Not RecruitingPhase 3
GlaxoSmithKline
Posted 6/10/2024

Rybrevant Demonstrates Promising Activity in Metastatic Colorectal Cancer

  • Rybrevant (amivantamab) plus chemotherapy achieved a 49% objective response rate (ORR) in RAS/BRAF wild-type metastatic colorectal cancer patients in the Phase II OrigAMI-1 study.
  • The combination therapy showed potential to render some patients eligible for curative surgery, suggesting a significant clinical benefit.
  • Johnson & Johnson plans to initiate two Phase III trials to further evaluate Rybrevant in colorectal cancer, expanding its potential therapeutic applications.
  • These findings support the strategy of targeting multiple oncogenic pathways with a single bispecific antibody, offering a novel approach to cancer treatment.

Aortic Valve Replacement Enhances Myocardial Perfusion and Exercise Capacity

  • Aortic valve replacement (AVR) improves myocardial perfusion and exercise capacity in patients with aortic stenosis.
  • The study used cardiovascular magnetic resonance to assess myocardial blood flow and cardiopulmonary exercise testing for exercise capacity.
  • AVR leads to reverse remodeling of the left ventricle and improved coronary microcirculation, enhancing overall cardiac function.
  • Findings support AVR as an effective intervention for improving cardiac physiology and exercise tolerance in aortic stenosis patients.

Pembrolizumab Plus Chemoradiotherapy Significantly Improves Overall Survival in Advanced Cervical Cancer

  • Phase 3 trial data presented at ESMO Congress show pembrolizumab plus chemoradiotherapy significantly improved overall survival (OS) in women with high-risk locally advanced cervical cancer.
  • The 36-month OS rate was 82.6% with pembrolizumab versus 74.8% with placebo, demonstrating a significant survival benefit (HR = 0.67; 95% CI, 0.5-0.9).
  • The FDA previously approved pembrolizumab plus chemoradiotherapy based on progression-free survival (PFS) data, and these OS results further support its use as a new standard of care.
  • While the pembrolizumab regimen had a manageable safety profile, a higher percentage of women experienced grade 3 or higher treatment-related adverse events (69.1% vs. 61.3%).

FDA Rejects MDMA-Assisted Therapy for PTSD, Sparking Controversy

  • The FDA has declined to approve MDMA-assisted therapy for PTSD, a decision that has sparked disappointment among researchers and advocates.
  • A Phase III study showed that 71% of participants receiving MDMA-assisted therapy no longer met the criteria for PTSD.
  • Lykos Therapeutics, the company overseeing the research, is pursuing all available regulatory pathways to address the FDA's concerns.
  • Experts argue that the decision is a setback for PTSD treatment, especially given the limitations and side effects of existing SSRI medications.

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