Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.

  title={Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.},
  author={Igor Puzanov and Mohammed M Milhem and David R. Minor and Omid Hamid and Ai Li and Lisa Chen and Michael A. Chastain and Kevin S. Gorski and Abraham A. Anderson and Jeffrey Chou and Howard L. Kaufman and Robert H. I. Andtbacka},
  journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
  volume={34 22},
  • I. PuzanovM. Milhem R. Andtbacka
  • Published 27 September 2016
  • Medicine, Biology
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma. METHODS In this open-label, multicenter, phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in week 1 (10(6) plaque-forming… 

Figures and Tables from this paper

Talimogene Laherparepvec combined with anti-PD-1 based immunotherapy for unresectable stage III-IV melanoma: a case series

The data suggest that combining checkpoint inhibitor(s) with T-VEC injection may provide a synergistic efficacy for patients with unresectable melanoma, and better overall response rate and complete response rate compared to published studies on similar therapeutic regimens.

Successful treatment with intralesional talimogene laherparepvec in two patients with immune checkpoint inhibitor-refractory, advanced-stage melanoma.

The successful treatment with intralesional T-VEC of two female patients with locoregionally advanced BRAF V600 wild-type melanoma who previously progressed on anti-PD-1 and anti-CTLA-4 inhibitors is reported on.

Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors

Early results in melanoma indicate that the combination of talimogene laherparepvec with ipilimumab or pembrolizumab has greater efficacy than either therapy alone, without additional safety concerns above those expected for each monotherapy.

Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study

The combination of T-VEC and pembrolizumab demonstrated a tolerable safety profile in R/M HNSCC and the efficacy with the combination was similar to that with pembrology monotherapy in historical H NSCC studies.

Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma—safety and efficacy in a phase II study

This combined immunotherapy is associated with adverse events similar to those associated with the respective monotherapies, however, this study does not provide any evidence of improved efficacy of the combination over ipilimumab alone.

The safety of talimogene laherparepvec for the treatment of advanced melanoma

This article sets out to review the use and safety and efficacy of T-VEC, an oncolytic herpes virus type I used as intralesional therapy for the treatment of unresectable metastatic melanoma in a cutaneous, subcutaneous, or nodal location.

Talimogene Laherparepvec (T-VEC): An Intralesional Cancer Immunotherapy for Advanced Melanoma

T-VEC is the first oncolytic viral immunotherapy to be approved for the local treatment of unresectable metastatic stage IIIB/C–IVM1a melanoma and it has been shown that intratumoral administration of this immunostimulatory agent successfully synergizes with immune checkpoint inhibitors.

Response to the Rechallenge With Talimogene Laherparepvec (T-VEC) After Ipilimumab/Nivolumab Treatment in Patient With Cutaneous Malignant Melanoma Who Initially Had a Progression on T-VEC With Pembrolizumab

After, initial progression on T-VEC with pembrolizumab, intervening immune checkpoints inhibitors may favorably modify the antitumor immunity and potentiate antitUMor effect of T- VEC rechallenge.

Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma.

  • J. ChesneyI. Puzanov H. Kaufman
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2018
The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilitationab alone, indicating that the combination has greater antitumor activity without additional safety concerns versus ipILimumab.

An Update on the Role of Talimogene Laherparepvec (T-VEC) in the Treatment of Melanoma: Best Practices and Future Directions

Preliminary data have demonstrated improved therapeutic responses to T-VEC in combination with immune checkpoint blockade in patients with melanoma without additive toxicity and identifies critical areas for clinical investigation to expand the role of T- VEC in combinations strategies for the treatment of melanoma and perhaps other cancers.



Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial.

Among patients with unresectable stage III or IV melanoma, treatment with ipilimumab plus sargramostim vs ipILimumab alone resulted in longer OS and lower toxicity, but no difference in PFS.

Improved survival with ipilimumab in patients with metastatic melanoma.

Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.

Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipILimumab alone, and in patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.

Ipilimumab Increases Activated T Cells and Enhances Humoral Immunity in Patients With Advanced Melanoma

It is suggested that ipilimumab can enhance immune responses mediated by different T-cell populations, and humoral immunity, in melanoma patients.

Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial

The trial shows that anti–CTLA-4 therapy has a tolerable safety profile in the presurgical setting and that a preoperative model can be used to obtain biological data on human immune responses, which can efficiently guide the monitoring of patients treated in the metastatic disease setting.

Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.

Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.

Immune Monitoring of the Circulation and the Tumor Microenvironment in Patients with Regionally Advanced Melanoma Receiving Neoadjuvant Ipilimumab

Neoadjuvant evaluation revealed a significant immunomodulating role for ipilimumab on Treg, MDSC and effector T cells in the circulation and tumor microenvironment that warrants further pursuit in the quest for optimizing melanoma immunotherapy.

Ipilimumab: controversies in its development, utility and autoimmune adverse events

  • J. Weber
  • Biology, Medicine
    Cancer Immunology, Immunotherapy
  • 2008
Favorable survival in patients with stage IV melanoma were observed that appear to be associated with unique side effects of the drug called “immune-related adverse events”, and the unusual kinetics of anti-tumor response with ipilimumab are described.

Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF.

Results show that this combination immunotherapy can induce the expansion not only of activated effector CD8 T cells in vivo but also of T cells that are specific for known tumor-associated antigens from the endogenous immune repertoire.

NK cells and CD8+ T cells cooperate to improve therapeutic responses in melanoma treated with interleukin-2 (IL-2) and CTLA-4 blockade

These results have implications for the design of clinical trials in patients with metastatic melanoma and provide new insights into how the immune system may be mediating anti-tumor activity with combination IL-2 and CTLA-4 blockade in melanoma.