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.

Abstract

TPS1110 Background: There are currently no curative treatments for patients with metastatic triple-negative breast cancer (mTNBC), and prognosis for this disease is very poor. Emerging treatment combinations of anti-programmed death ligand 1 (PD-L1) agents with chemotherapy have shown promise in mTNBC. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1, which is highly expressed in breast cancer cells. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death (ICD). Preliminary results from an ongoing phase 1 study of LV monotherapy has shown LV to be well tolerated and to have encouraging antitumor activity in patients with mTNBC. Combining LV and pembrolizumab may result in complementary, as well as synergistic, activity through LV-induced ICD that creates a microenvironment favorable for enhanced anti-PD-L1 activity. Methods: This single-arm, open-label, phase 1b/2 study evaluates the safety and antitumor activity of LV in combination with pembrolizumab as first-line therapy for patients with unresectable locally advanced or mTNBC (NCT03310957, 2017-002289-35). Patients must have measureable disease per RECIST v1.1, an ECOG score of 0 or 1, and no prior cytotoxic or anti-PD-L1 treatment for advanced disease. This study has 2 parts that are enrolling sequentially: a dose-finding phase that starts at LV 2.5 mg/kg + pembrolizumab 200 mg intravenously every three weeks, and a dose expansion phase. The primary objectives are to evaluate the safety/tolerability and objective response rate of LV + pembrolizumab, and identify the recommended phase 2 dose of LV. The secondary objectives are to assess duration of response, disease control rate, progression-free survival, and overall survival. Additional objectives include assessing PD-L1 and LIV-1 expression-response relationship. Study enrollment is ongoing in the US and EU. Clinical trial information: NCT03310957.

Antibody–drug conjugates in solid tumors: a look into novel targets

“…Nevertheless, preclinical evidence in TNBC cell lines showed also that LV is capable of inducing an effective immunogenic cell death (ICD), so ideally increasing the potential benefit of immunotherapy [ 63 ]. The combination of pembrolizumab and LV is currently under investigation as first-line therapy for mTNBC in the phase I/II SGNLVA-002 [ 64 ], while one arm of the Morpheus-TNBC trial is evaluating the administration of atezolizumab plus LV as second-line treatment. Finally, LV is under investigation in the phase II SGNLVA-005 study [ 65 ], enrolling patient with advanced solid tumors in different tumor-specific cohorts (GC and GEJ adenocarcinoma, esophageal squamous cell carcinoma, SCLC, squamous-NSCLC, non-squamous-NSCLC and head and neck squamous cell carcinoma).…”

Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody–drug conjugates in the breast cancer treatment landscape

“…The majority of combination trials investigate the combination of SG or T-DXd with ICIs, based on the preclinical and clinical data supporting the combination of ADC and ICI. 58 , 61 , 62 Other ongoing trials evaluate combinations with other anticancer treatments, among which are PARPi, endocrine agents or other HER2-directed therapies. The high interest results in a dynamic clinical trial landscape for both drugs, with currently 11 and 12 recruiting clinical trials for SG and T-DXd, respectively, including two phase III trials for both drugs.…”

Triple‑negative breast cancer therapy: Current and future perspectives (Review)

“…It was for first-line treatment of patients with unresectable locally advanced or metastatic TNBC. Initial dose-finding studies revealed ORR of 35% with responses independent of PD-L1 status and manageable toxicity (106).…”