Dataset Information

A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer.

ABSTRACT:

Purpose

Neoadjuvant combination immune checkpoint blockade and intralesional oncolytic virotherapy have the potential to activate antitumor responses in patients with breast cancer.

Experimental design

Eligibility for this pilot phase I trial included patients with localized HER2-negative breast cancer who received systemic nivolumab and ipilimumab and intratumor talimogene laherparepvec (T-VEC; NCT04185311). The primary objective was to evaluate the safety and adverse event profile of immunotherapy combined with T-VEC in patients with localized, HER2-negative breast cancer.

Results

Six patients were enrolled, 4 having relapses after prior neoadjuvant chemotherapy and 2 who were previously untreated. Toxicities included 1 patient having grade 3 hypotension and type 1 diabetes mellitus, 3 patients with hypothyroidism, and all patients having constitutional symptoms known to be associated with the administration of T-VEC. One patient had a pathologic complete response, 3 patients had pathologic partial responses, 1 showed no significant response, and 1 had disease progression. Biopsies demonstrated increased immune cell infiltration in samples from patients who responded to therapy.

Conclusions

This triple immunotherapy regimen provided responses in patients with advanced or relapsed HER2-negative breast cancer, at the expense of long-term toxicities.

Significance

Systemic immune checkpoint blockade with a programmed death receptor 1 and a CTL antigen-4 blocking antibody, combined with intralesional oncolytic virotherapy, is a chemotherapy-free combination aimed at inducing an antitumor immune response locally and systemic immunity.

SUBMITTER: Nguyen VP

PROVIDER: S-EPMC10445661 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer.

Nguyen Vina P VP Campbell Katie M KM Nowicki Theodore S TS Elumalai Nila N Medina Egmidio E Baselga-Carretero Ignacio I DiNome Maggie L ML Chang Helena R HR Oseguera Denise K DK Ribas Antoni A Glaspy John A JA

Cancer research communications 20230823 8

<h4>Purpose</h4>Neoadjuvant combination immune checkpoint blockade and intralesional oncolytic virotherapy have the potential to activate antitumor responses in patients with breast cancer.<h4>Experimental design</h4>Eligibility for this pilot phase I trial included patients with localized HER2-negative breast cancer who received systemic nivolumab and ipilimumab and intratumor talimogene laherparepvec (T-VEC; NCT04185311). The primary objective was to evaluate the safety and adverse event profi ...[more]

PMID: 37621406

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Project description:We conducted the first trial of neoadjuvant PD-1 blockade in resectable non-small cell lung cancer (NSCLC), finding nivolumab monotherapy to be safe and feasible with an encouraging rate of pathologic response. Building on these results, and promising data for nivolumab plus ipilimumab (anti-CTLA-4) in advanced NSCLC, we expanded our study to include an arm investigating neoadjuvant nivolumab plus ipilimumab. Patients with resectable stage IB (≥4 cm)-IIIA (American Joint Committee on Cancer Tumor Node Metastases seventh edition), histologically confirmed, treatment-naïve NSCLC received nivolumab 3 mg/kg intravenously plus ipilimumab 1 mg/kg intravenously 6 weeks prior to planned resection. Nivolumab 3 mg/kg was given again approximately 4 and 2 weeks preoperatively. Primary endpoints were safety and feasibility with a planned enrollment of 15 patients. Pathologic response was a key secondary endpoint. While the treatment regimen was feasible per protocol, due to toxicity, the study arm was terminated early by investigator consensus after 9 of 15 patients were enrolled. All patients received every scheduled dose of therapy and were fit for planned surgery; however, 6 of 9 (67%) experienced treatment-related adverse events (TRAEs) and 3 (33%) experienced grade ≥3 TRAEs. Three of 9 patients (33%) had biopsy-confirmed tumor progression precluding definitive surgery. Of the 6 patients who underwent resection, 3 are alive and disease-free, 2 experienced recurrence and are actively receiving systemic treatment, and one died postoperatively due to acute respiratory distress syndrome. Two patients who underwent resection had tumor pathologic complete responses (pCRs) and continue to remain disease-free over 24 months since surgery. Pathologic response correlated with pre-treatment tumor PD-L1 expression, but not tumor mutation burden. Tumor KRAS/STK11 co-mutations were identified in 5 of 9 patients (59%), of whom two with disease progression precluding surgery had tumor KRAS/STK11/KEAP1 co-mutations. Though treatment was feasible, due to toxicity the study arm was terminated early by investigator consensus. In light of this, and while the long-term disease-free status of patients who achieved pCR is encouraging, further investigation of neoadjuvant nivolumab plus ipilimumab in patients with resectable NSCLC requires the identification of predictive biomarkers that enrich for response.

Dataset Information

A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer.

Purpose

Experimental design

Results

Conclusions

Significance

Publications

A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer.

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