“Sacituzumab govitecan (IMMU-132) was well tolerated and demonstrated early and durable responses in heavily pretreated patients with metastatic triple-negative breast cancer (mTNBC), according to the results of a recent phase I/II study published in the Journal of Clinical Oncology.
“Sacituzumab govitecan is an antibody–drug conjugate that targets Trop-2, which is expressed in more than 90% of TNBCs, by selectively delivering SN-38, the active metabolite of irinotecan. It was granted a breakthrough therapy designation by the FDA in February 2016 for the treatment of patients with mTNBC, following at least 2 treatments for metastatic disease.”
“Investigators are seeking to determine whether the addition of ABT-414, an antibody–drug conjugate, to concomitant radiotherapy and temozolomide will improve the survival of patients with newly diagnosed glioblastoma multiforme (GBM) with epidermal growth factor receptor (EGFR) amplification.
“The phase IIb/III Intellance1 trial (NCT02573324), which is currently recruiting participants, seeks to randomize approximately 720 patients to a 2-phase experimental arm with ABT-414 or to a placebo comparator arm. Participants in the experimental arm will receive intravenous ABT-414 combined with standard therapy of oral temozolomide and radiation in a chemoradiation treatment phase, followed by ABT-414 plus oral temozolomide during an adjuvant treatment phase. The comparator arm will follow the same regimens, with an intravenous placebo to replace ABT-414.”
“The antibody-drug conjugate sacituzumab govitecan (IMMU-132) produced high objective response rates, many of them quite durable, in a multicenter study of heavily pretreated patients with metastatic triple-negative breast cancer, presented at the 2016 San Antonio Breast Cancer Symposium.
“Trop-2 is a calcium signal transducer that drives tumor growth and has shown promise as a novel therapeutic target in triple-negative breast cancer, since the majority of these tumors express Trop-2. Sacituzumab govitecan targets Trop-2 and selectively delivers high doses of SN-38, the active metabolite of irinotecan that is 1,000 times more active than the parent compound. In addition to drug delivery, sacituzumab govitecan potentially also activates antibody-dependent cell-mediated cytotoxicity.”
“After decades of frustration, efforts to develop antibodies that can ferry drugs into cancer cells — and minimize damage to healthy tissue — are gathering steam. The next generation of these ‘weaponized antibody’ therapies, called antibody–drug conjugates (ADCs), is working its way through clinical trials.
“Researchers will gather to discuss this renaissance on 30 November at the Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany. The improvements come after the first wave of experimental ADCs failed to deliver on its promise.
” ‘Initially there was a lot of excitement, and then slowly many of them did not work,’ says Raffit Hassan, a cancer researcher at the US National Cancer Institute in Bethesda, Maryland. Now, he says, there are two new ADCs in phase III clinical trials, and many more in earlier-stage testing.”
“Phase 1 study results presented at the 21st Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO) demonstrated the antibody drug conjugate ABT-414 has shown promising results for the treatment of patients with EGFR-amplified, recurrent glioblastoma (GBM).
“Lead author Martin van den Bent, MD, PhD, of the Erasmus MC Cancer Center in Rotterdam, the Netherlands, is presenting the findings during the SNO meeting, which was held November 17-20, 2016, in Scottsdale, Arizona.
“In an interview with Targeted Oncology, van den Bent discussed the trial’s significant findings, that agent’s toxicity profile, and what lies ahead for the investigational agent.”
“A novel HER2-targeting antibody-drug conjugate showed promising antitumor activity across multiple tumor types, including HER2-postive breast cancer, according to phase I data presented at the 2016 ESMO Congress.
” ‘Antibody-drug conjugates represent promising drugs with a wider therapeutic window by effecting efficient and specific drug delivery to oncogene expressing tumor cells,’ explained lead author Kenji Tamura, MD, PhD, chairman, Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.”
“Findings from a highly anticipated, randomized, phase II trial could possibly pave the path for the FDA approval of the first targeted therapy for patients with triple-negative breast cancer (TNBC), explains Linda T. Vahdat, MD.
“The METRIC study is exploring the efficacy and safety of glembatumumab vedotin (CDX-011) versus standard capecitabine in this subset of patients, particularly in those with high levels of glycoprotein NMB (gpNMB) expression (NCT01997333).
“The antibody-drug conjugate is a novel approach designed to target a very difficult-to-treat patient population, whose sole approved treatment option is standard chemotherapy, Vahdat stresses.”
Written by Emma Shtivelman, PhD and Dov Shiffman, PhD
The American Society of Clinical Oncology (ASCO) meeting of 2016 is behind us, but oncologists, patients, and journalists are still analyzing the most interesting presentations made there. Below, we describe some of the more prominent results in triple negative breast cancer (TNBC), both promising and disappointing.
“Immunomedics, Inc., (IMMU) today announced that sacituzumab govitecan (IMMU-132), its lead investigational antibody-drug conjugate (ADC), shrank tumors by 30% or more initially in 26% (12/46) of evaluable patients with metastatic non-small-cell lung cancer (NSCLC), with a later confirmed overall objective response rate (ORR) of 13%, in accordance with RECIST 1.1 criteria. For the patients with confirmed responses, the duration of response (DOR) was 9 months.
“Interim median progression-free survival (PFS) and overall survival (OS) were 3.9 months (95% confidence interval [CI]; 3.4, 6.9) and 10.5 months (95% CI; 5.8, 10.5), respectively. Significant tumor shrinkage and disease stabilization was observed in both adenocarcinoma and squamous cell carcinomas, the two major subtypes of NSCLC, and in patients who had failed previous anti-PD-1/PD-L1 therapy.”
Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.