Early safety from phase 1b/3, multicenter, open-label, randomized trial of talimogene laherparepvec (T-VEC) + pembrolizumab (pembro) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): MASTERKEY-232

Harrington, Kevin J.; Kong, Anthony; Mach, Nicolas; Rordorf, Tamara; Corral, J.; Espeli, Vittoria; Treichel, Sheryl; Cheng, Jonathan D.; Kim, J.J.; Chesney, Jason

doi:10.1093/annonc/mdx374.061

Cited by 7 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In summary, talimogene laherparepvec showed efficacy in two patients with advanced melanoma who had disease progression following multiple previous systemic therapies and had a toxicity profile consistent with previously reported clinical trials. Phase 1/3 clinical trials of talimogene laherparepvec in combination with pembrolizumab for the treatment of melanoma and squamous cell carcinoma of the head and neck are ongoing 15 , 16 . In addition, a phase 1 trial of intrahepatic injection of talimogene laherparepvec for the treatment of liver tumors is also currently evaluating the first patient cohort.…”

Section: Discussionmentioning

confidence: 99%

“…The observation reported here that a talimogene laherparepvec–injected dermal metastasis had significant CD4 + and CD8 + T cell infiltration indicates that talimogene laherparepvec may induce tumor immunity. Talimogene laherparepvec, alone or in combination with immune checkpoint inhibitors, may have utility as treatment for multiple solid tumor types 15 – 19 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors

et al. 2018

View full text Add to dashboard Cite

Talimogene laherparepvec is a genetically modified herpes simplex virus type 1–based oncolytic immunotherapy for the local treatment of unresectable subcutaneous and nodal tumors in patients with melanoma recurrent after initial surgery. We report on two patients with melanoma who, after progression on numerous systemic therapies, derived clinical benefit from talimogene laherparepvec in an expanded-access protocol (ClinicalTrials.gov, NCT02147951). Intralesional talimogene laherparepvec (day 1, ≤4 ml 106 PFU/ml; after 3 weeks, ≤4 ml 108 PFU/ml every 2 weeks) was administered until complete response, no injectable tumors, progressive disease, or intolerance occurred. Patient 1 was 71 years old, had stage IIIB disease, and had previously received granulocyte–macrophage colony-stimulating factor, vemurafenib, metformin, ipilimumab, dabrafenib, trametinib, and pembrolizumab. Patient 2 was 45 years old, had stage IIIC disease, and had previously received nivolumab/ipilimumab combination therapy. There were marked reductions in the number and size of melanoma lesions during treatment with talimogene laherparepvec. Both patients experienced mild-to-moderate nausea and vomiting, which were managed using ondansetron, metoclopramide, and pantoprazole. Both patients completed treatment with talimogene laherparepvec in the expanded-access protocol on 24 November 2015, but received talimogene laherparepvec in clinical practice. Patient 1 continues to receive therapy (>60 weeks); patient 2 experienced a complete response at 23 weeks. Immunohistochemistry of a biopsied dermal metastasis from patient 1 showed a marked infiltration of CD4+ and CD8+ T cells after 1 year of treatment. Talimogene laherparepvec was active in patients with advanced melanoma with disease progression following multiple previous systemic therapies; no new safety signals were identified.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors

et al. 2018

View full text Add to dashboard Cite

show abstract

“…IO-IO: Checkpoint + innate immune activationMASTERKEY-232 (NCT02626000)Phase 1b/3. Combination pembrolizumab + talimogene laherparepvec (T-VEC) as second-line therapy in R/M HNSCC patients.T-VEC is the first FDA-approved oncolytic immunotherapy which works to systemically enhance the antitumor immune response [132] [133]. Twenty-four (66.7%) patients experienced a grade 3 or higher TRAE, with 5 related to T-VEC and 3 related to Pembrolizumab.…”

Section: Key Clinical Questionsmentioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Cohen¹,

Bell²,

Bifulco³

et al. 2019

j. immunotherapy cancer

522

422

View full text Add to dashboard Cite

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals – the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab – for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a ≥ 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score ≥ 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians’ understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S. Electronic supplementary material The online version of this article (10.1186/s40425-019-0662-5) contains supplementary material, which is available to authorized users.

show abstract

“…MASTERKEY-232 was a phase I trial using pembrolizumab and T-vec for HNSCC. 35 The response rate was 16.7%, with substantial toxicity (Table 4). There are several possible reasons to explain the negative results of MASTERKEY-232.…”

Section: Oncolytic Virusmentioning

confidence: 99%

“…However, data in HNSCC are not as encouraging. MASTERKEY‐232 was a phase I trial using pembrolizumab and T‐vec for HNSCC . The response rate was 16.7%, with substantial toxicity (Table ).…”

Section: Combination Therapy For Hnsccmentioning

confidence: 99%

Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

Kao

Lou

2019

Head & Neck

View full text Add to dashboard Cite

Background Immune checkpoint inhibitors (ICIs) can reinvigorate T cells and activate the immune system to eliminate cancer cells. Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a poor prognosis. The roles of ICIs for HNSCC treatments are emerging. Method We reviewed the study results of Programmed‐Death 1 (PD‐1) and PD‐ligand‐1 (PD‐L1) monoclonal antibodies for HNSCC. The ongoing trials of anti‐PD‐1 and anti‐PD‐L1 were also reviewed. Results Nivolumab showed a significant overall survival benefit in platinum‐refractory HNSCC patients. For platinum‐sensitive or first‐line patients, pembrolizumab monotherapy (patients with PD‐L1 Combined Positive Score ≥ 20) or pembrolizumab‐platinum‐fluorouracil improved overall survival vs the EXTREME (cetuximab‐platinum‐fluorouracil). Many HNSCC studies have combined anti‐PD1/PD‐L1 therapy with various anticancer agents or radiotherapy to improve treatment efficacy. Conclusion ICIs demonstrate their efficacies for R/M HNSCC patients. The incorporation of ICIs showed a great impact on the treatment landscape of HNSCC.

show abstract

Early safety from phase 1b/3, multicenter, open-label, randomized trial of talimogene laherparepvec (T-VEC) + pembrolizumab (pembro) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): MASTERKEY-232

Cited by 7 publications

References 0 publications

Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors

Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

Contact Info

Product

Resources

About