Erivedge (vismodegib) / Curis, Roche - LARVOL DELTA

Phase 2 Trial of Vismodegib in Advanced Cancers with Hedgehog pathway alterations (ESMO 2025) - No abstract available

Metastases • P2 data • Oncology

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Ulrik Lassen | Trial completion date: Apr 2025 ➔ Apr 2030 | Trial primary completion date: Apr 2024 ➔ Apr 2029

Trial completion date • Trial primary completion date • Oncology

Aggressive Basal Cell Carcinoma With Rib Metastasis: An Uncommon Presentation of a Common Skin Cancer. (PubMed, Cureus) - "The patient was managed with a multimodal approach, including hedgehog pathway inhibition with vismodegib, immune checkpoint blockade with cemiplimab, palliative radiation therapy, and ultimately extensive surgical resection. The coordinated therapeutic response led to clinical improvement and disease stabilization. This case underscores the potential aggressiveness of neglected BCC and reinforces the value of early detection and comprehensive, multidisciplinary management in advanced presentations."

Journal • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer

Quantifying the Role of Specialty Medications in Medicare Part D Expenditures in Dermatology. (PubMed, JAMA Dermatol) - "New therapies approved after 2013 (Otezla, Cosentyx, Taltz, Dupixent, Tremfya, Skyrizi, and Odomzo) accounted for 69.5% of all spending growth. Prescription rates increased more slowly for older specialty drugs (Humira, Enbrel, Stelara, and Erivedge), but their prices increased more (9.2% annually) than prices for newer agents...While the price of the average dermatologic medication has increased rapidly, this primarily reflects increased prescribing of newly introduced specialty drugs. While these therapies expand treatment options, their rising share of costs highlights the need for policies that balance innovation, access, and affordability."

Journal • Medicare • Reimbursement • US reimbursement • Dermatology

Cryotherapy as a salvage therapy to Vismodegib in a patient with a giant, refractory, locally advanced, oculofacial Basal Cell Carcinoma . A case from a private office in a Greek small town. (EADV 2025) - No abstract available

Clinical • Metastases • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Type VII secretion system gene mutations driving global mycobacterium tuberculosis transmission revealed by whole genomic sequence. (PubMed, Front Cell Infect Microbiol) - "Specifically, we identified one risk mutation (espA(Rv3616c, 4055801)) in L1, four risk mutations (espK(Rv3879c, 4357597), esxU(Rv3445c, 3863138), esxO(Rv2346c, 2626018), and esxW(Rv3620c, 4060588)) in L2, and four risk mutations (eccE1(Rv3882c, 4362807), espE(Rv3864, 4340330), espA(Rv3616c, 4055993), and eccC5(Rv1783, 2019942)) in L4...Our findings suggest that mutations in ESX genes play a crucial role in Mycobacterium tuberculosis transmission. These results can be applied to the development of novel strategies for the treatment and prevention of disease."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Remarkable Response to Vismodegib in a Locally Advanced Basal Cell Carcinoma on the Nose. (PubMed, Cutis) - "Vismodegib, an Hh inhibitor, is approved by the US Food and Drug Administration for treatment of locally advanced or metastatic BCC. This case report details the successful management of a large BCC on the nose of an elderly patient using vismodegib."

Journal • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Advanced Basal Cell Carcinoma: A Narrative Review on Current Systemic Treatments and the Neoadjuvant Approach. (PubMed, J Pers Med) - P2 | " The pivotal phase II trials ERIVANCE and BOLT investigated the efficacy and safety profile of vismodegib and sonidegib, respectively, with reported objective response rates (ORRs) of 60.3% and 56% in laBCC patients, respectively. The pivotal phase II trial NCT03132636 investigated the efficacy and safety profile of cemiplimab in patients who progressed or were intolerant to prior HHI therapy, with an ORR of 32.1% in laBCC patients...Several phase I/II clinical trials are currently investigating HHIs and immune-checkpoint inhibitors in the neoadjuvant setting followed by surgery for aBCC patients, with the aim of providing more favorable treatment outcomes, especially when upfront surgery would result in functional and/or aesthetic sequelae. Advanced BCC treatment is challenging, and the neoadjuvant approach followed by surgery is expected to reduce surgical complexity, increase tissue preservation, and improve patients' satisfaction."

Journal • Review • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Long-Term Success in the Management of an Extensive Medial Canthal Basal-Cell Carcinoma with Vismodegib. (PubMed, J Curr Ophthalmol) - "No treatment-related side effects were observed. This case demonstrates the clinical value of vismodegib in advanced periocular BCC, particularly when surgery is inappropriate or declined by the patient."

Journal • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Nodular Basal Cell Carcinoma

Importance of Carnitine in Dermatology (CDA 2025) - "Topically, carnitine has shown efficacy in reducing sebum, decreasing hyperpigmentation post- laser treatment, improving skin tolerability with adapalene in acne, reducing acne severity, and enhancing quality of life...Orally, carnitine has proven effective in reducing inflammation, alleviating isotretinoin-related liver and muscle effects, easing muscle spasms in vismodegib patients, countering wasting in pemphigus vulgaris during glucocorticoid therapy, and improving adipocytokines, mental health and inflammatory markers in PCOS. It has also shown benefits in preventing cardiomyopathy progression in severe recessive dystrophic epidermolysis bullosa, reducing advanced glycation end products, and improving walking distance and ulcer healing in peripheral vascular disease. Conclusion Carnitine and its derivatives have therapeutic potential in dermatology, offering benefits both topically and orally, warranting further exploration of their clinical applications."

Acne Vulgaris • Atopic Dermatitis • Cardiomyopathy • Cardiovascular • Complement-mediated Rare Disorders • Dermatitis • Dermatology • Fibrosis • Hereditary Angioedema • Immunology • Infectious Disease • Melanoma • Metabolic Disorders • Pemphigus Vulgaris • Peripheral Arterial Disease • Polycystic Ovary Syndrome • Primary Immunodeficiency • Pruritus • Psoriasis • Sarcoidosis • Scleroderma • Solid Tumor • Systemic Sclerosis

Vismodegib Combined With Atezolizumab in Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Ronald Buckanovich | Trial completion date: Apr 2028 ➔ Mar 2033 | Trial primary completion date: Apr 2028 ➔ Mar 2031

Platinum resistant • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • BRCA • CD4

Prevalence of genetic alterations in basal cell carcinoma patients resistant to Hedgehog pathway inhibitors: a systematic review. (PubMed, Ann Med) - "We included three prospective cohort studies encompassing 27 samples, all of which were resistant to vismodegib treatment...This systematic review highlights the prevalence of genetic alterations in the Hh pathway in BCC and offers insights into the mechanisms involved in treatment resistance. Understanding the high resistance rates of these genes may facilitate the development of more effective targeted therapies for BCC."

Journal • Review • Basal Cell Carcinoma • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • PTCH1 • TP53

Breaking barriers: exploring blood-brain barrier crossing mechanisms with nanomedicine for effective glioma treatment. (PubMed, 3 Biotech) - "Polymeric nanocapsules (PNCs) encapsulating Methotrexate significantly reduced tumor volumes in animal models of glioma. Additionally, fucoidan-encapsulated Vismodegib nanoparticles effectively crossed the BBB and exhibited minimal toxicity in healthy brain tissue...Despite the success in preclinical studies, challenges remain regarding nanoparticle biocompatibility, off-target effects, and regulatory approval. Nevertheless, these findings support the potential of multifunctional nanomedicines for glioma therapy by enabling BBB penetration, immune modulation, and targeted drug delivery, which can be further improved."

IO biomarker • Journal • Review • Brain Cancer • Glioma • Immune Modulation • Immunology • Oncology • Solid Tumor

Eight-Year Experience of Hedgehog Pathway Inhibitors at Three Tertiary Referral Centres in the Australian State of Victoria. (PubMed, Australas J Dermatol) - "Secondary acquired drug resistance occurred in 77% (10/13) of locally advanced and metastatic BCC patients after a median duration of 13 months. Further work is needed to optimise the neoadjuvant use of Hedgehog inhibitors with radiotherapy or surgery given poor long-term Hedgehog inhibitor tolerability and to develop strategies to counteract the issue of acquired resistance."

Journal • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

CUPISCO: A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site (clinicaltrials.gov) - P2 | N=528 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2024

Trial completion • Trial completion date • Oncology

Docking for Smoothened antagonist chemotypes not susceptible to a vismodegib-resistance mutation. (PubMed, Eur J Med Chem) - "Antagonizing SMO has been recognized as a therapeutic strategy exemplified by drugs such as vismodegib and sonidegib, but despite initial remission, cancer recurrence is frequent due to resistance mutations. The mutation affects potency and maximal inhibitory effect of these ligands only in a way similar to SANT-1, a SMO ligand unencumbered by the mutation. Our study thus shows a successful application of structure-based design for the discovery of novel SMO antagonist chemotypes."

Journal • Oncology

A phase II trial of perioperative oral itraconazole for the management of low risk basal cell carcinoma. (ASCO 2025) - P=N/A | "Funded by No funding sources reported Clinical Trial Registration Number: NCT03972748 Background: Recently, new treatment options have emerged for advanced basal cell carcinoma (BCC), including oral Hedgehog pathway inhibitors like Vismodegib. Preoperative oral Itraconazole demonstrated both clinical and molecular activity in localized, low-risk BCC lesions, with no patients showing disease progression and two patients exhibiting partial and complete responses, respectively. The median tumor diameter significantly decreased after the treatment period. In addition to the reduction in tumor size, there was a notable decrease in the expression of CD105, marking the first study to demonstrate this correlation in this context."

P2 data • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • ENG

Comparison of the tolerability and safety of hedgehog inhibitors in real-life: A cohort of 330 patients with locally advanced basal cell carcinoma. (ASCO 2025) - "Funded by No funding sources reported Background: Two hedgehog pathway inhibitors (HHIs) have been approved for the treatment of locally advanced basal cell carcinoma (laBCC): vismodegib and sonidegib. We present here the largest real-life comparison of HHIs in a real-life cohort of laBCC patients. The cumulative incidence of the first AE was significantly lower with sonidegib. Even though the range of AEs was similar with both HHIs, dysgeusia and cramps were less frequent with sonidegib."

Clinical • Metastases • Alopecia • Basal Cell Carcinoma • Immunology • Non-melanoma Skin Cancer • Oncology

Adverse events associated with vismodegib: insights from a real-world pharmacovigilance study using the FAERS database. (PubMed, Front Pharmacol) - "This study provides valuable insights into the real-world safety profile of vismodegib. It not only confirms the known adverse events on the label, but also suggests several potential novel adverse events, thereby supporting a more informed and rational use of vismodegib in clinical practice."

Adverse events • Journal • Real-world evidence • Alopecia • Basal Cell Carcinoma • Fatigue • Gastrointestinal Disorder • Immunology • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma

Hedgehog inhibitors exert anti-proliferation effects and synergistically interact with trastuzumab in HER2-positive gastric cancer models. (PubMed, Acta Oncol) - "This study highlights the potential of combining Hh inhibitors with trastuzumab as a therapeutic strategy for HER2-positive GC by targeting the AKT/mTOR pathway."

Journal • Preclinical • Gastric Cancer • Oncology • Solid Tumor • HER-2 • SMO

Alternate Dosing Regimens for Vismodegib: A Literature Review. (PubMed, Curr Treat Options Oncol) - "Intermittent dosing of vismodegib may be more appropriate for patients with locally advanced BCC and drug holidays may be more suited for patients with basal cell nevus syndrome. The most appropriate strategy in each case though will ultimately depend on patient preference."

Journal • Review • Alopecia • Basal Cell Carcinoma • Fatigue • Non-melanoma Skin Cancer • Oncology • Rare Diseases

Uncovering the genetic basis of therapy resistance in gorlin syndrome: A rare downstream mutation and the shift to second-line treatment (SID 2025) - "The patient's prior treatment included vismodegib for nine non-consecutive months; however, therapy was discontinued primarily due to lack of efficacy as well as the development of minor adverse effects. The patient is currently undergoing treatment with twice-daily topical 5-fluorouracil and monthly photodynamic therapy (PDT) and continues to show a good clinical response without significant adverse effects at monthly follow-ups. This case highlights the critical role of genetic testing in patients with suspected Gorlin syndrome, particularly in guiding treatment decisions and identifying mutations that may impact therapeutic response."

Clinical • Late-breaking abstract • Aesthetic Medicine • Basal Cell Carcinoma • Brain Cancer • Cardiovascular • Dermatology • Genetic Disorders • Hypertension • Medulloblastoma • Non-melanoma Skin Cancer • Obesity • Oncology • Solid Tumor • PTCH1

DELINEATING THE ROLE OF HEDGEHOG SIGNALING PATHWAY IN PANCREATIC STELLATE CELLS DURING CHRONIC PANCREATITIS (DDW 2025) - "In a separate experiment, PSCs were harvested from healthy mice pancreas and activated using TGFβ with or without concomitant treatment with Hh pathway inhibitor, Vismodegib... Our scRNAseq analysis revealed PSC specific activation of Hh signaling in CP, accompanied by identification of novel markers of PSC activation. Hh pathway inhibition mediates PSC quiescence by downregulation of these pro-fibrotic genes."

Fibrosis • Gastrointestinal Disorder • Immunology • Inflammation • Pancreatitis • ATF3 • IGFBP7 • NR4A1 • TGFB1

Adverse events associated with vismodegib: insights from a real-world pharmacovigilance study using the FAERS database (Frontiers) - "A total of 7,733 adverse event reports associated with vismodegib were identified from the FDA Adverse Event Reporting System database. Data mining identified positive signals for on-label adverse events, such as muscle spasms, taste alterations, alopecia, fatigue, and weight decreased. Notably, potential off-label adverse events including squamous cell carcinoma, dehydration and dysphagia were also detected. The median time to onset for these adverse events was 69 days post-drug administration, highlighting the importance of close monitoring, particularly within the initial 2 months of treatment."

Clinical • Oncology