Imlygic (talimogene laherparepvec) / Amgen - LARVOL DELTA

Combination of talimogene laherparepvec (T-VEC) with atezolizumab (atezo) in patients (pts) with residual breast cancer (BC) after standard neoadjuvant chemotherapy (NAC): Survival results of the SOLTI-PROMETEO study (ESMO-BC 2025) - P1 | "Adjuvant treatments included chemotherapy (n=6), endocrine therapy (n=19), and abemaciclib (n=1). Despite the limited sample size, this analysis of PROMETEO suggests that achieving a pCR with T-VEC and atezo in pts with RD after standard multi-agent CT is associated with improved survival outcomes. These results underscore the potential of trials with this design to identify effective drugs for escalating treatment in poor-prognosis populations of pts with HER2- BC."

Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

When standard therapies are not an option: T-VEC for lentigo maligna melanoma of the head (ADO 2026) - No abstract available

Melanoma • Solid Tumor

Primary results of SOLTI-1503 PROMETEO phase 2 trial of Combination of Talimogene Laherparepvec (T-VEC) with Atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy (SABCS 2022) - P1 | "Two months of T-VEC in combination with atezolizumab induced a pCR in a subgroup of pts with chemoresistant HER2- breast cancer. This effect is probably related to the immune activation provoked by the combined treatment. Interestingly, a high discrepancy was observed between the pre-surgical radiological imaging and the actual surgical pathological report."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1 • TMB

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. (PubMed, J Clin Oncol) - "T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone."

Clinical • Journal • P3 data • Melanoma • Oncology • Solid Tumor

Interim analysis of a phase II study of talimogene laherparepvec (T-VEC) followed by combination T-VEC + nivolumab in non-melanoma skin cancers and refractory cutaneous lymphoma (NCI#10057) (SITC 2024) - "Conclusions Analysis of data from Part I of this clinical trial suggests that T-VEC monotherapy did not translate to broad clinical efficacy across all tumor types, though may show activity in patients without visceral metastases. MCC and CSCC expansion cohorts (Part II) will be reported separately.View this table:View inline View popup Download powerpoint Abstract 621 Table 1 Best response to T-VEC monotherapyDownload figure Open in new tab Download powerpoint Abstract 621 Figure 1 Elderly female with at least 4 in-transit metastases from MCC on the left lower leg, who achieved a durable PR on T-VEC monotherapy"

IO biomarker • P2 data • Hematological Malignancies • Lymphoma • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CCL23 • CTAG1B • TRB

Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial. (PubMed, J Immunother Cancer) - P1b/2 | "No new safety signals were reported.At the 5-year follow-up, the improved response rates observed with T-VEC plus ipilimumab were durable. This is the first randomized controlled study of the combination of an oncolytic virus and a checkpoint inhibitor that meets its primary end point.Trial registration number: NCT01740297."

Combination therapy • Journal • Metastases • P2 data • Melanoma • Oncology • Solid Tumor

Vaccines for Cancer: A Translational Science Review. (PubMed, JAMA) - "Sipuleucel-T, a vaccine against the antigen prostatic acid phosphatase, reduced all-cause mortality compared with placebo in men with metastatic castrate-resistant prostate cancer (32% vs 23%; hazard ratio, 0.78 [95% CI, 0.61-0.98]; P = .03). Compared with granulocyte-macrophage colony-stimulating factor, a systemic immune stimulant, talimogene laherparepvec increased rates of a 6-month or longer complete or partial response, defined as the disappearance of all treated disease and at least a 50% decrease in the sum of the products of perpendicular diameters of the measurable lesion with no new lesions, respectively, when injected into advanced melanoma lesions (16.3% [95% CI, 12.1%-20.5%] vs 2.1% [95% CI, 0%-4.5%]; odds ratio, 8.9; P < .001)...Combining the personalized mutation-based messenger RNA (mRNA) vaccine (mRNA-4157) with the immune checkpoint inhibitor pembrolizumab for resected high-risk stage IIIB to IV cutaneous melanoma improved relapse-free survival..."

IO biomarker • Journal • Bladder Cancer • Castration-Resistant Prostate Cancer • Cutaneous Melanoma • Fatigue • Genito-urinary Cancer • Hepatitis B • Infectious Disease • Melanoma • Oncology • Prostate Cancer • Solid Tumor • ACPP • PSAP

When standard therapies are not an option: T-VEC for lentigo maligna melanoma of the head (ADO 2026) - No abstract available

Melanoma • Solid Tumor

Engineering HSV-1 for Gene Therapy, Oncolytic Immunotherapy, and Neuroscience. (PubMed, Virol Sin) - "Clinical successes such as T-VEC, G47Δ, and B-VEC have validated the clinical potential of HSV-1 engineering, yet broader translation remains limited by antiviral immunity, inefficient delivery, epigenetic silencing, genome instability, and manufacturing challenges. In this review, we illustrate how HSV-1 has evolved from a naturally neurotropic virus into a versatile biomedical tool, whose therapeutic and research potential emerges from the precise matching of viral properties with disease-specific requirements, delivery contexts, and functional objectives."

Journal • Review • Gene Therapies • Herpes Simplex

Combination of talimogene laherparepvec (T-VEC) with pembrolizumab (pembro) in advanced melanoma patients following progression on a prior PD-1 inhibitor: SWOG S1607 (AACR 2023) - "Translational study is ongoing for pharmacodynamic confirmation. T-VEC plus pembro in melanoma patients who have progressed on prior anti-PD1/L1 therapy has efficacy in the subset of melanoma patients who have non-visceral metastases.$$table_{B77E4652-270A-4849-8205-FBD28FD53F6E}$$Table 1Cohort A (Visceral)Cohort B(Non-Visceral)N (%; 95% CI)1127Confirmed PR + CR0 (0%; 0%-28%)7 (26%; 11%-46%)Confirmed + Unconfirmed1 (9%; 0%-41%)9 (33%; 17%-54%)Durable response0 (0%; 0%-28%)4 (15%; 4%-34%)Median PFS in months2.1 (0.7-5.5)2.3 (1.9-6.2)INJECTED LESIONS1127Confirmed PR + CR0 (0%; 0%-28%)6 (22%; 9%-42%)Confirmed + Unconfirmed, PR + CR1 (9%; 0%-41%)8 (30%; 14%-50%)NON-INJECTED, NON-VISCERAL LESIONS819Confirmed PR + CR0 (0%; 0%-37%)3 (16%; 3%-40%)Confirmed + Unconfirmed, PR + CR0 (0%; 0%-37%)5 (26%; 9%-51%)VISCERAL LESIONS11Confirmed PR + CR0 (0%; 0%-28%)Confirmed + Unconfirmed, PR + CR1 (9%; 0%-41%)ACQUIRED RESISTANCE32Confirmed PR + CR0 (0%; 0%-71%)2 (100%; 16%-100%)Confirmed..."

Clinical • IO biomarker • Metastases • Tumor mutational burden • Melanoma • Oncology • Solid Tumor • TMB

Complete tumour regression of in-transit melanoma following discontinuation of talimogene laherparepvec. (PubMed, BMJ Case Rep) - "After excision, the final pathology showed no residual melanoma, indicating a delayed, complete pathological response to T-VEC. This case may reflect the potential for continued or delayed anti-tumour immune activity after cessation of T-VEC and support further investigation into T-VEC's immune effects and timing of treatment in neoadjuvant settings."

Journal • Cardiovascular • Dermatology • Fatigue • Genetic Disorders • Herpes Simplex • Melanoma • Oncology • Pain • Skin Cancer • Solid Tumor

Oncolytic Virotherapy, Long Stalled, Nears Second Approval. (PubMed, Cancer Discov) - "Nearly 11 years after T-VEC became the first oncolytic virus approved in a major market, the closest candidate to follow it-Replimune's RP1, now facing an FDA advisory committee-remains a locally injected herpesvirus for melanoma, underscoring how little the field has advanced. Researchers blame a stack of unresolved obstacles-flawed trial designs, mistimed drug combinations, tumor defenses, such as hypoxia, and the inability to deliver most viruses intravenously-even as smarter sequencing, neoadjuvant approaches, and a bladder-cancer virus near approval hint at renewed momentum."

Journal • Bladder Cancer • Genito-urinary Cancer • Melanoma • Oncology • Solid Tumor

In silico clinical trials of BiTE expression by oncolytic viruses reveal the impact of patient heterogeneity on dosage protocol. (PubMed, PLoS Comput Biol) - "Furthermore, we find that if individuals are classified as non-responders to the Phase II T-VEC clinical protocol, they may respond to more frequent administration of lower dosages. This work highlights how in silico clinical trials can provide predictions for novel therapeutics to generate hypotheses and guide the design of treatment schedules for clinical translation."

Heterogeneity • IO biomarker • Journal • Infectious Disease • Measles • Oncology

Neoadjuvant Intralesional Injection of Talimogene Laherparepvec (clinicaltrials.gov) - P2 | N=2 | Active, not recruiting | Sponsor: John Rieth | Trial completion date: Mar 2030 ➔ Feb 2031 | Trial primary completion date: Jun 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

A Study of Talimogene Laherparepvec (T-VEC) in Combination With Pembrolizumab in Patients With Metastatic and/or Locally Advanced Sarcoma (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Angiosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Oncolytic Viruses in Cancer Therapy: Mechanisms, Challenges, and Emerging Clinical Applications. (PubMed, Ann Pharm Fr) - "Several OVs, such as herpes simplex virus 1 (HSV-1), human adenovirus type 5 (HAdV-C5), mammalian orthoreovirus type 3 Dearing strain (T3D; pelareorep), and Vaccinia virus-derived platforms (e.g., JX-594/Pexa-Vec), have shown significant therapeutic efficacy. Among them, Talimogene laherparepvec (T-VEC) (a genetically engineered HSV-1) has been approved by the Food and Drug Administration for melanoma treatment...OVT offers a dual-action therapeutic approach and holds significant promise in the field of precision oncology. Continued innovation and clinical validation are essential for its widespread adoption in cancer care."

Journal • Review • Herpes Simplex • Melanoma • Oncology • Solid Tumor

Outcomes of Talimogene Laherparepvec in Soft Tissue Sarcoma. (PubMed, J Surg Oncol) - "This case series of patients receiving T-VEC for sarcoma adds to the literature of intralesional therapies for this rare disease. Our experience suggests that T-VEC may be administered safely and may provide local tumor control in select patients with sarcoma who have failed prior therapy with ICI."

Journal • Oncology • Rare Diseases • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy. (PubMed, Eur J Cancer) - "For ITM unresectable melanoma, first-line anti-PD1, T-VEC, and BRAF(/MEK)i can induce clinically meaningful and durable responses. The optimal treatment choice depends on patient and disease characteristics and preferences."

Journal • Melanoma • Oncology • Solid Tumor

The Evolving Role of Intralesional Therapy in In-Transit Melanoma. (PubMed, Curr Oncol) - "Platforms such as talimogene laherparepvec (T-VEC), vusolimogene oderparepvec (RP1), and tavokinogene telseplasmid with electroporation (Tavo-EP) demonstrate enhanced activity in combination with checkpoint blockade, whereas therapies limited to pattern-recognition receptor activation have shown inconsistent efficacy in randomized trials. Emerging noninvasive technologies, such as focused ultrasound, may further expand strategies for remodeling the immunosuppressive tumor microenvironment to enable immune sensitization. These findings support a shift toward mechanism-based treatment selection in which locoregional therapies function to overcome immune resistance rather than solely reduce tumor burden."

Journal • Review • Melanoma • Oncology • Solid Tumor

Vaccines as treatment for melanoma: an update review. (PubMed, Front Immunol) - "Among these, Talimogene laherparevec (T-VEC) is the sole vaccine that has received approval from the U.S. Food and Drug Administration (FDA) for melanoma treatment...Within future therapeutic frameworks, melanoma vaccines are envisioned to play a key role by inducing and amplifying a targeted T-cell response against cancer. This approach is particularly suited for combination with other immunotherapies that neutralize the resistance mechanisms found in the tumor microenvironment."

Journal • Review • Melanoma • Oncology • Solid Tumor

Updates on intratumoral therapies in melanoma. (PubMed, Cancer) - "Talimogene laherparepvec, a genetically modified herpes simplex virus type 1-encoding granulocyte-macrophage colony-stimulating factor, was the first oncolytic viral therapy approved in a solid tumor indication...Emerging trends include image-guided visceral injection, combinatorial regimens, and the integration of intratumoral therapy in the neoadjuvant setting. As these therapies evolve, intratumoral approaches may expand their role in melanoma management, bridging locoregional tumor control with systemic immune activation and complementing existing systemic treatments."

Journal • Review • Herpes Simplex • Melanoma • Oncology • Solid Tumor

Emerging Oncolytic Viruses: Beyond Adenoviruses and Herpes Simplex Virus. (PubMed, J Cancer) - "The field has garnered substantial attention following the regulatory approval of talimogene laherparepvec (T-VEC), a genetically engineered herpes simplex virus, for metastatic melanoma treatment-a watershed moment in oncolytic virotherapy. Recent advances in genetic engineering have significantly enhanced OV specificity and efficacy, addressing critical challenges including tumor-selective targeting and immune evasion. This review comprehensively examines the complex mechanisms underlying OV therapeutic action, clinical applications, and recent developments that position oncolytic virotherapy as a transformative strategy in contemporary cancer treatment."

Journal • Review • Herpes Simplex • Melanoma • Oncology • Solid Tumor

Talimogene Laherparepvec in advanced-stage vulvar and vaginal melanoma: a case report (WAGO 2026) - "The patient underwent initial systemic treatment with combination Ipilimumab/Nivolumab...The patient underwent neoadjuvant stereotactic body radiation to the vagina followed by 3 cycles of Pembrolizumab...In two cases presented above, intratumoral T-VEC resulted in complete tumor regression. This novel drug is a highly-active, durable treatment option for unresectable melanoma, and is feasible for use in the Gynecologic Oncology setting."

Case report • Clinical • Metastases • Cutaneous Melanoma • Gynecologic Cancers • Melanoma • Oncology • Solid Tumor • Vulvar Cancer

Intratumoral oncolytic virotherapy in pancreatic cancer: from feasibility to immune priming. (PubMed, Transl Gastroenterol Hepatol) - No abstract available

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Acral lentiginous melanoma metastases to the vitreous masquerading as uveitis: A case report. (PubMed, Am J Ophthalmol Case Rep) - "This is an 86-year-old Caucasian female with Stage III Acral Lentiginous Melanoma of the left heel who was initiated on nivolumab and relatlimab along with intralesional talimogene laherparepvec (TVEC)...She was diagnosed elsewhere with unilateral acute intermediate uveitis, leading to discontinuation of immunotherapy and initiation of topical difluprednate...The patient underwent a therapeutic pars plana vitrectomy, intravitreal melphalan injection, and ocular radiotherapy, with resolution of vitreous metastasis. Several atypical, red flags in this patient may serve as clinical indicators; history of malignancy with locoregional progression, timing of immune CPI therapy to symptom onset, failure to treatment response, and large white, amelanotic vitreous cells arranged in veils. This case emphasizes the importance of maintaining a broad differential diagnosis in patients with atypical, or treatment resistant uveitis, especially in individuals with known underlying..."

Journal • Cutaneous Melanoma • Immunology • Melanoma • Ocular Inflammation • Oncology • Ophthalmology • Solid Tumor • Uveitis