A Phase I Trial of Talimogene Laherparepvec in Combination with Neoadjuvant Chemotherapy for the Treatment of Nonmetastatic Triple-Negative Breast Cancer

Soliman, Hatem; Hogue, Deanna; Han, Hyo S.; Mooney, Blaise; Costa, Ricardo; Lee, Marie Catherine; Niell, Bethany L.; Williams, Angela; Chau, Alec; Falcon, Shannon; Khakpour, Nazanin; Weinfurtner, R. Jared; Hoover, Susan; Kiluk, John V.; Rosa, Marilin; Khong, Hung T.; Czerniecki, Brian J.

doi:10.1158/1078-0432.ccr-20-3105

Cited by 41 publications

(26 citation statements)

References 18 publications

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“…A previous study showed that tumor-infiltrating lymphocytes in breast cancer are associated with better response to neoadjuvant chemotherapy 21 ; thus, intratumoral injection of T-VEC may generate a favorable tumor microenvironment to enhance response to chemotherapy. Indeed, a recent phase I trial of T-VEC combined with neoadjuvant chemotherapy for stage II–III triple-negative breast cancer showed a pathologic complete response rate of 55%, which was higher than the rate of 30–40% expected with neoadjuvant chemotherapy alone 22 . T-VEC was injected intratumorally with intravenous paclitaxel up to 5 times, followed by doxorubicin/cyclophosphamide.…”

Section: Discussionmentioning

confidence: 83%

A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

Kai

Marx

Liu

et al. 2021

Sci Rep

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Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3–8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63–NA) and 361 days (95% CI, 240–NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.

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Section: Discussionmentioning

confidence: 83%

A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

Kai

Marx

Liu

et al. 2021

Sci Rep

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show abstract

“…A previous study showed that tumorin ltrating lymphocytes in breast cancer are associated with better response to neoadjuvant chemotherapy [23]; thus, intratumoral injection of T-VEC may generate a favorable tumor microenvironment to enhance response to chemotherapy. Indeed, a recent phase I trial of T-VEC combined with neoadjuvant chemotherapy for stage II-III triple-negative breast cancer showed a pathologic complete response rate of 55%, which was higher than the rate of 30%-40% expected with neoadjuvant chemotherapy alone [24]. T-VEC was injected intratumorally with intravenous paclitaxel up to 5 times, followed by doxorubicin/cyclophosphamide.…”

Section: Discussionmentioning

confidence: 99%

A Phase II Study of Talimogene Laherparepvec for Patients With Inoperable Locoregional Recurrence of Breast Cancer

Kai

Marx

Liu

et al. 2021

Preprint

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Purpose: Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer.Methods: Patients had to have cutaneous, subcutaneous, or nodal tumors injectable with T-VEC. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥3). Local lesions were photographed before each cycle.Results: Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3-8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63-NA) and 361 days (95% CI, 240-NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n=7, 78%).Conclusion: None of the patients was able to complete the planned 10 cycles due to the disease progression. Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.Trial registration number and date of registration: ClinicalTrials.gov Identifier: NCT02658812; registered [January 14, 2016]

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“…Given the infiltrating effect of OVs on tumor cells and immune cell activation of ICIs, the combination of OVs and ICIs is used in more than 30% of the clinical trials with active status. According to a previous study on T-Vec combined with pembrolizumab, Ribas et al found that intratumoral injection of a modified OV to enhance immune recognition produced a high response rate in patients with advanced melanoma [99]. The confirmed objective response rate of 62% and complete response rate of 33% for each immune-related response criterion in 21 patients that received this combination of therapy suggested that OVs could enhance the efficacy of anti-PD-1 therapy by altering the TME.…”

Section: Combination Of Ovs and Icismentioning

confidence: 96%

Emerging systemic delivery strategies of oncolytic viruses: A key step toward cancer immunotherapy

et al. 2022

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Oncolytic virotherapy (OVT) is a novel type of immunotherapy that induces anti-tumor responses through selective selfreplication within cancer cells and oncolytic virus (OV)-mediated immunostimulation. Notably, talimogene laherparepvec (T-Vec) developed by the Amgen company in 2015, is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment. However, the systemic administration of OVs still faces huge challenges, including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy. Recently, state-of-the-art progress has been made in the development of systemic delivery of OVs, which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery. Herein, this review describes the general characteristics of OVs, focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT. The emerging multiple systemic administration approaches of OVs are summarized in the past five years. In addition, the combination treatments between OVT and traditional therapies (chemotherapy, thermotherapy, immunotherapy, and radiotherapy, etc.) are highlighted. Last but not least, the future prospects and challenges of OVT are also discussed, with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.

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A Phase I Trial of Talimogene Laherparepvec in Combination with Neoadjuvant Chemotherapy for the Treatment of Nonmetastatic Triple-Negative Breast Cancer

Cited by 41 publications

References 18 publications

A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

A Phase II Study of Talimogene Laherparepvec for Patients With Inoperable Locoregional Recurrence of Breast Cancer

Emerging systemic delivery strategies of oncolytic viruses: A key step toward cancer immunotherapy

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