Clinical Trial News

Dato-DXd plus durvalumab achieved a 50% overall pathologic complete response (pCR) rate in stage II/III high-risk HER2-negative breast cancer patients, according to the I-SPY 2.2 trial. The study highlights the utility of evaluating treatment response by response predictive subtype (RPS), with further investigation needed in immune-positive and hormone receptor–negative/DNA damage repair deficiency–negative subtypes. The combination showed promising results in the immune-positive and triple-negative subtypes, with over 50% of pCRs achieved by the end of block A, avoiding standard chemotherapy.

Dr. Manuela Schmidinger discussed three abstracts at the 2024 ESMO meeting on kidney cancer, focusing on the TiNivo-2, LITESPARK-005, and SUNNIFORECAST trials. TiNivo-2 found no superiority of tivozanib + nivolumab over tivozanib monotherapy in RCC patients post-IO therapy. LITESPARK-005 showed belzutifan maintained progression-free survival over everolimus but lacked overall survival benefit. SUNNIFORECAST indicated nivolumab + ipilimumab improved overall survival in non-clear cell RCC compared to standard care, though with trial heterogeneity challenges.

Morgan Stanley's Terence Flynn maintains a Sell rating on BMY stock due to potential FDA labeling concerns for KarXT, despite high anticipation for its schizophrenia treatment approval. Flynn anticipates a 5% stock decrease if KarXT's label includes restrictive measures, and significant growth hinges on KarXT's Alzheimer's disease psychosis indication or ABBV's emraclidine failure. Barclays also assigns a Sell rating with a $42.00 price target.

T-DXd, with or without pembrolizumab and fluoropyrimidine, showed antitumor activity and manageable safety in HER2-positive esophageal, gastric, and GEJ cancer patients. Full-dose T-DXd and fluoropyrimidine had the highest ORR (78%), while pembrolizumab-containing arms showed higher toxicities. Reduced-dose triplets demonstrated manageable safety.

Dr. Jonathan E. Rosenberg presented 5-year follow-up results of the EV-103 Study at the 2024 ESMO Congress, showing durable responses and meaningful survival outcomes with Enfortumab Vedotin (EV) + Pembrolizumab in cisplatin-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC), with a median overall survival (OS) of 26 months and 41.5% of patients alive at 5 years.

iTeos Therapeutics' mid-stage trial results show its drug, when combined with GSK's immunotherapy, shrank lung tumors in twice as many patients compared to GSK's therapy alone. The trial raised safety concerns due to three treatment-related deaths from immune-related inflammation. Despite previous failures of TIGIT-targeting drugs, iTeos' data could rekindle interest in the target, with further data expected to clarify the combination's impact on survival and disease progression.

J&J's Rybrevant shows promise in colorectal cancer, with Phase II data suggesting it makes metastatic patients eligible for curative surgery, leading to a 49% ORR in the OrigAMI-1 study.

Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis, impact of left ventricular hypertrophy in aortic valve stenosis, prognostic value of coronary flow reserve in asymptomatic moderate or severe aortic stenosis, determinants and functional significance of myocardial perfusion reserve in severe aortic stenosis, mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries, coronary microvascular dysfunction, left ventricular remodeling, and clinical outcomes in aortic stenosis, long-term prognostic role of coronary flow velocity reserve in patients with aortic valve stenosis, sex-related differences in left ventricular remodeling in severe aortic stenosis and reverse remodeling after aortic valve replacement, reverse myocardial remodeling following valve replacement in patients with aortic stenosis, association between type 2 diabetes and changes in myocardial structure, contractile function, energetics, and blood flow before and after aortic valve replacement in patients with severe aortic stenosis, impact of patient-prosthesis mismatch and aortic valve design on coronary flow reserve after aortic valve replacement, myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction, predicting outcome after valve replacement, American society of echocardiography recommendations for use of echocardiography in clinical trials, a minimum dataset for a standard transoesophageal echocardiogram, myocardial perfusion cardiovascular magnetic resonance: optimized dual sequence and reconstruction for quantification, myocardial blood flow quantification with MRI by model-independent deconvolution, EAPCI expert consensus document on Ischaemia with non-obstructive coronary arteries, optimizing the exercise protocol for cardiopulmonary assessment, calcific aortic stenosis: a disease of the valve and the myocardium, functional changes in coronary microcirculation after valve replacement in patients with aortic stenosis, angina pectoris in patients with aortic stenosis and normal coronary arteries: mechanisms and pathophysiological concepts, demystifying complex coronary hemodynamics in patients undergoing transcatheter aortic valve replacement, impaired hyperemic myocardial blood flow is associated with subclinical systolic dysfunction and myocardial injury in aortic stenosis, coronary artery disease and outcomes of aortic valve replacement for severe aortic stenosis, observed and relative survival after aortic valve replacement, predictors of mortality after aortic valve replacement, 2020 ACC/AHA guideline for the management of patients with valvular heart disease, 2021 ESC/EACTS Guidelines for the management of valvular heart disease, impact of diabetes on remodelling, microvascular function and exercise capacity in aortic stenosis, residual compromised myocardial contractile reserve after valve replacement for aortic stenosis, cardiopulmonary exercise testing for evaluation of a randomized exercise training intervention following aortic valve replacement, effects of aortic valve replacement on exercise duration and functional status in adults with valvular aortic stenosis, coronary physiology during exercise and vasodilation in the healthy heart and in severe aortic stenosis, impaired coronary and myocardial flow in severe aortic stenosis is associated with increased apoptosis, early aortic valve replacement improves exercise capacity in truly asymptomatic patients with severe aortic stenosis.

Pembrolizumab plus chemoradiotherapy significantly improved OS for women with high-risk locally advanced cervical cancer, making it the new standard of care.

A Boulder-based therapist is disappointed by the FDA's decision not to approve MDMA-assisted therapy for PTSD, despite a Phase III study showing 71% of participants no longer met PTSD criteria. The therapist argues the decision is a setback for PTSD sufferers, who often face severe symptoms and suicidal thoughts. The FDA's decision may be due to a lack of precedent for approving a therapy rather than just a drug.