Meeting News CoveragePerspective

Sacituzumab govitecan shows promise for metastatic NSCLC

Treatment with sacituzumab govitecan induced objective responses and appeared tolerable in patients with metastatic non–small cell lung cancer who had received first-line platinum-based therapy, according to the results from an expansion cohort of a phase 1/2 study presented at the ASCO Annual Meeting.

This therapy showed efficacy for squamous and non-squamous patients as well as for patients with prior PD-1/PD-L1 therapy,” D. Ross Camidge, MD, PhD, professor in the division of medical oncology and Joyce Zeff chair in lung cancer research at University of Colorado Anschutz Medical Campus, said during a presentation.

Sacituzumab govitecan (IMMU-132, Immunomedics) is an antibody drug conjugate comprised of SN-38 — the active metabolite of irinotecan, a topoisomerase inhibitor — conjugated to an anti–Trop-2 humanized monoclonal antibody.

Trop-2 expression is greater than 80% in most epithelial cancers, including NSCLC.

Camidge and colleagues evaluated the efficacy and safety of sacituzumab govitecan in 34 patients (median age, 62.5 years; men, n = 21) with metastatic NSCLC who had received first-line therapy and were enrolled in an expansion cohort of a phase 1/phase 2 clinical trial.

Most patients (n = 29) had an ECOG performance status score of 1, whereas four had a score of 0 and one had an unknown score. Patients had received a median of three prior lines of chemotherapy (range, 1-7).

All patients received sacituzumab govitecan on days 1 and 8 of a 21-day treatment cycle and underwent tolerance assessments weekly and progression assessments every 8 weeks.

Researchers assigned sacituzumab govitecan in 8-mg/kg (n = 9) or 10-mg/kg (n = 25) doses.

Objective response rate — which included confirmed and unconfirmed responses — was 31% for both dosage groups, 37% for the 8-mg/kg group, and 29% for the 10-mg/kg group.

Thirty-five percent of patients experienced a clinical benefit — defined as a partial response plus stable disease for at least 6 months — at a rate of 50% in the 8-mg/kg arm and 33% in the 10-mg/kg arm.

Median PFS was 3.9 months in the total population, 4.2 months in the 8-mg/kg arm and 3.8 months in the 10-mg/kg arm.

Median OS was not reached in the total study population or either dosage subgroup.

Twenty-four patients have experienced an adverse event. The most common grade three or worse drug-related adverse events included diarrhea (8%) and neutropenia (8%).

No patient developed antibodies, detected via enzyme-linked immunosorbent assay, to the antibody or the drug.

“This therapy has several options to its parent therapy,” Camidge said during a presentation. “Those advantages appear to included enhanced response and reduced toxicity, but further research is required to evaluated safety and efficacy of IMMU-132.” by Nick Andrews

References:

Camidge DR, et al. Abstract 9011. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclos ure: Camidge reports no relevant financial disclosures. Other researchers report honoraria and research funding from, as well as consultant/advisory roles and employment with, Immunomedics. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

Treatment with sacituzumab govitecan induced objective responses and appeared tolerable in patients with metastatic non–small cell lung cancer who had received first-line platinum-based therapy, according to the results from an expansion cohort of a phase 1/2 study presented at the ASCO Annual Meeting.

This therapy showed efficacy for squamous and non-squamous patients as well as for patients with prior PD-1/PD-L1 therapy,” D. Ross Camidge, MD, PhD, professor in the division of medical oncology and Joyce Zeff chair in lung cancer research at University of Colorado Anschutz Medical Campus, said during a presentation.

Sacituzumab govitecan (IMMU-132, Immunomedics) is an antibody drug conjugate comprised of SN-38 — the active metabolite of irinotecan, a topoisomerase inhibitor — conjugated to an anti–Trop-2 humanized monoclonal antibody.

Trop-2 expression is greater than 80% in most epithelial cancers, including NSCLC.

Camidge and colleagues evaluated the efficacy and safety of sacituzumab govitecan in 34 patients (median age, 62.5 years; men, n = 21) with metastatic NSCLC who had received first-line therapy and were enrolled in an expansion cohort of a phase 1/phase 2 clinical trial.

Most patients (n = 29) had an ECOG performance status score of 1, whereas four had a score of 0 and one had an unknown score. Patients had received a median of three prior lines of chemotherapy (range, 1-7).

All patients received sacituzumab govitecan on days 1 and 8 of a 21-day treatment cycle and underwent tolerance assessments weekly and progression assessments every 8 weeks.

Researchers assigned sacituzumab govitecan in 8-mg/kg (n = 9) or 10-mg/kg (n = 25) doses.

Objective response rate — which included confirmed and unconfirmed responses — was 31% for both dosage groups, 37% for the 8-mg/kg group, and 29% for the 10-mg/kg group.

Thirty-five percent of patients experienced a clinical benefit — defined as a partial response plus stable disease for at least 6 months — at a rate of 50% in the 8-mg/kg arm and 33% in the 10-mg/kg arm.

Median PFS was 3.9 months in the total population, 4.2 months in the 8-mg/kg arm and 3.8 months in the 10-mg/kg arm.

Median OS was not reached in the total study population or either dosage subgroup.

Twenty-four patients have experienced an adverse event. The most common grade three or worse drug-related adverse events included diarrhea (8%) and neutropenia (8%).

No patient developed antibodies, detected via enzyme-linked immunosorbent assay, to the antibody or the drug.

“This therapy has several options to its parent therapy,” Camidge said during a presentation. “Those advantages appear to included enhanced response and reduced toxicity, but further research is required to evaluated safety and efficacy of IMMU-132.” by Nick Andrews

References:

Camidge DR, et al. Abstract 9011. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclos ure: Camidge reports no relevant financial disclosures. Other researchers report honoraria and research funding from, as well as consultant/advisory roles and employment with, Immunomedics. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

    Perspective
    Grace Dy

    Grace Dy

    Although the confirmed response rate was only 13% — at least a third of the patients with “unconfirmed partial response” had early disease progression — this study demonstrates the feasibility and potential clinical efficacy of antibody-drug conjugate (ADC) therapies in lung cancer. Although irinotecan typically induces severe diarrhea in about a quarter to a third of patients when administered systemically, when its active metabolite SN-38 is delivered as the cytotoxic payload of this ADC, the frequency of severe diarrhea appears to be significantly reduced. This makes intuitive sense as ADCs represent a “targeted” approach to delivering cytotoxic chemotherapy.

    However, since it is essentially still chemotherapy, it appears that the responses seen may not be durable in contrast to immunotherapy with checkpoint inhibitory agents.

    Nonetheless, there are multiple ADCs currently in development in lung cancer, and we hope that at least one ADC will demonstrate sufficient clinical activity and superior therapeutic index compared with traditional chemotherapy to be in routine clinical practice within the next few years.

    • Grace Dy, MD
    • Roswell Park Cancer Institute

    Disclosures: Dy reports no relevant financial disclosures.

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