SGNLVA-002: Single arm, open label, phase Ib/II study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of patients with unresectable locally-advanced or metastatic triple-negative breast cancer

Boni, Valentina; Alemany, Carlos; Meisel, Jane L.; Sinha, Rajni; Sterrenberg, Danielle; Tkaczuk, Katherine; Wang, Y.; Wang, Z.; Han, HS

doi:10.1093/annonc/mdz100.047

Cited by 9 publications

(2 citation statements)

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“…92 SGN-LIV1A is being evaluated both as a monotherapy and in combination with immunotherapy agents. 93,94 Trastuzumab duocarmazine (SYD985), previously mentioned, is also being examined in combination with Paclitaxel in the context of TNBC (NCT04602117). 95,96 Another noteworthy ADC is MGC018, which employs an anti-B7-H3 antibody linked to a duocarmycin payload.…”

Section: Future Perspectivesmentioning

confidence: 99%

Antibody-Drug Conjugates in Breast Cancer: A Comprehensive Review of How to Selectively Deliver Payloads

Monteiro,

Nunes,

Junior

et al. 2024

BCTT

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Antibody-drug conjugates (ADCs) have surfaced as a promising group of anticancer agents employing the precise targeting capacity of monoclonal antibodies to transport highly effective cytotoxic payloads. Compared to conventional chemotherapy, they aim to selectively eradicate cancer cells while minimizing off-target toxicity on healthy tissues. An increasing body of evidence has provided support for the efficacy of ADCs in treating breast cancer across various contexts and tumor subtypes, resulting in significant changes in clinical practice. Nevertheless, unlocking the full potential of these therapeutic agents demands innovative molecular designs to address complex clinical challenges, including drug resistance, tumor heterogeneity, and treatment-related adverse events. This thorough review provides an in-depth analysis of the clinical data on ADCs, offering crucial insights from pivotal clinical trials that assess the efficacy of ADCs in diverse breast cancer settings. This aids in providing a comprehensive understanding of the current state of ADCs in breast cancer therapy, while also providing valuable perspectives for the future.

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Section: Future Perspectivesmentioning

confidence: 99%

Antibody-Drug Conjugates in Breast Cancer: A Comprehensive Review of How to Selectively Deliver Payloads

Monteiro,

Nunes,

Junior

et al. 2024

BCTT

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“…[55][56][57] There are currently ongoing trials combining sacituzumab govitecan with pembrolizumab and atezolizumab in mTNBC, ladiratuzumab vedotin and pembrolizumab, trastuzumabderuxtecan and durvalumab, and a second TROP2 ADC, datopotamab-deruxtecan and durvalumab. [58][59][60][61][62] Preliminary results are encouraging.…”

Section: Combination With Antibody-drug Conjugatesmentioning

confidence: 99%

Role of Immunotherapy in Breast Cancer

Jacob

Huppert

Rugo

2023

JCO Oncology Practice

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The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of solid tumor malignancies. In breast cancer, the most robust data to date for ICI exist for triple-negative breast cancer (TNBC). Preclinical studies suggested increased antitumoral immune response in patients with TNBC undergoing ICI treatment. Early clinical trials investigated the use of ICI monotherapy in patients with metastatic TNBC with promising results, particularly in the first-line setting and for those patients whose tumors had high programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) expression. Subsequent trials evaluated the use of ICI in combination with conventional chemotherapy to enhance the host immune response. Pembrolizumab combined with chemotherapy in the KEYNOTE-355 study resulted in improved progression-free survival and overall survival benefits for patients with PD-L1 combined positive score > 10 metastatic TNBC. In early-stage disease, two phase III trials demonstrated increased rates of pathologic complete response at the time of surgery with the addition of neoadjuvant ICI to standard chemotherapy. The large KEYNOTE-522 trial showed improved event-free survival with neoadjuvant and adjuvant ICI. Several biomarkers have been identified, which may be predictive of response to ICI therapy including PD-1/PD-L1 expression, tumor mutational burden, tumor-infiltrating lymphocytes, and multigene assays capturing favorable immune cell signatures. For hormone receptor–positive and human epidermal growth factor receptor–positive breast cancer, there are ongoing studies evaluating ICI therapy in combination with chemotherapy and targeted agents. Finally, across all subtypes, several novel immunotherapeutic agents are under investigation including novel ICIs, cancer vaccines, adoptive cellular therapy, and oncolytic viruses.

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