Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases

Hecht, Joel Randolph; Raman, Steven Satish; Chan, Arlene; Kalinsky, Kevin; Baurain, Jean François; Martín Jiménez, Miguel; Martinez-García, Maria; Berger, Martin D.; Lauer, Ulrich M.; Khattak, Adnan; Carrato, Alfredo; Zhang, Yue; Liu, Kate; Cha, Edward; Keegan, Alissa; Bhatta, Sumita; Strassburg, Christian P.; Roohullah, Aflah

Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases

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dc.contributor.author Hecht, Joel Randolph
dc.contributor.author Raman, Steven Satish
dc.contributor.author Chan, Arlene
dc.contributor.author Kalinsky, Kevin
dc.contributor.author Baurain, Jean François
dc.contributor.author Martín Jiménez, Miguel
dc.contributor.author Martinez-García, Maria
dc.contributor.author Berger, Martin D.
dc.contributor.author Lauer, Ulrich M.
dc.contributor.author Khattak, Adnan
dc.contributor.author Carrato, Alfredo
dc.contributor.author Zhang, Yue
dc.contributor.author Liu, Kate
dc.contributor.author Cha, Edward
dc.contributor.author Keegan, Alissa
dc.contributor.author Bhatta, Sumita
dc.contributor.author Strassburg, Christian P.
dc.contributor.author Roohullah, Aflah
dc.date.accessioned 2024-04-15T06:22:03Z
dc.date.available 2024-04-15T06:22:03Z
dc.date.issued 2023
dc.description.abstract Highlights Safety/efficacy of T-VEC + atezolizumab was explored in patients with triple negative breast cancer or colorectal cancer. Limited evidence of antitumor activity was observed from the combination of atezolizumab and T-VEC injected into the liver. The safety profile reflected known risks with T-VEC, with no unexpected findings from the addition of atezolizumab. Background Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases. Methods In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs. Results Between 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable. Conclusions The safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.
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dc.identifier.citation Hecht JR, Raman SS, Chan A, Kalinsky K, Baurain JF, Jimenez MM, et al. Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases. ESMO Open. 2023 Apr;8(2):100884. DOI: 10.1016/j.esmoop.2023.100884
dc.identifier.doi http://dx.doi.org/10.1016/j.esmoop.2023.100884
dc.identifier.issn 2059-7029
dc.identifier.uri http://hdl.handle.net/10230/59756
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof ESMO Open. 2023 Apr;8(2):100884
dc.rights © 2023 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CCBY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Breast neoplasms
dc.subject.keyword Drug therapy combination
dc.subject.keyword Gastrointestinal neoplasms
dc.subject.keyword Virotherapyviral immunotherapy
dc.title Phase Ib study of talimogene laherparepvec in combination with atezolizumab in patients with triple negative breast cancer and colorectal cancer with liver metastases
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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