Immunomedics Inc. Announces Objective Responses in Five Types of Solid Cancer With IMMU-132
Jun 2 14
Immunomedics Inc. reported that 71% of patients (34 of 48) with diverse metastatic solid cancers had durable disease stabilization after receiving treatments with the Company's novel investigational antibody-drug conjugate (ADC), IMMU-132. These include 7 patients (15%) with colorectal, small-cell and non-small-cell lung, esophageal, and triple-negative breast cancers showing partial responses with tumor shrinkage of 30% or more as measured by computed tomography (CT). IMMU-132 is made up of SN-38, the active metabolite of irinotecan, conjugated to the Company's humanized anti-TROP-2 antibody. In patients who relapsed or were refractive to prior topoisomerase I or II inhibitors, this ADC demonstrated subsequent activity, suggesting that it can overcome resistance to such inhibitors, including irinotecan. Even after failing multiple prior therapies, a median time to progression of at least 12.6 weeks (range 6.0-51.4 weeks) was observed in 48 patients with at least 1 CT assessment. One patient with hormone-refractive prostate cancer has a long-term, durable stable disease response, which is approaching a year. This patient has received 30 doses of IMMU-132 and treatment is continuing. Despite repeated dosing, no antibodies against the ADC, neither to the antibody nor to SN-38, have been detected in this or any other patients. A total of 69 patients with a median of 3 prior therapies have been enrolled into the multicenter trial, including 13 patients with pancreatic cancer. The Phase I/II results were presented by Alexander Starodub, M.D., Ph.D., of Indiana University Health Goshen Center for Cancer Care, Goshen, IN, at the 2014 Annual Meeting of the American Society of Clinical Oncology in Chicago, IL. Earlier at the same Annual Meeting, the Company also presented preclinical studies on the characterization of IMMU-132. In animals given the ADC, nearly all of the SN-38 was found to remain bound to the antibody during blood circulation. As such, IMMU-132 is not toxic to the animal but maintains SN-38 in a latent, toxic form to be released upon binding to the TROP-2 antigen on the tumor cells and internalized. In contrast, when irinotecan is converted to SN-38, a significant amount of the metabolite is detoxified. As a result, IMMU-132 delivered 120-times higher amounts of SN-38 to the tumors compared to irinotecan at its maximum tolerated dose. This corroborates the higher therapeutic index believed to be achieved with IMMU-132 in the clinical studies. In a variety of human cancers grafted to mice, the ADC produced a broad spectrum of tumor-growth-inhibition activities, even at doses well below the maximum tolerated doses in the animal. More importantly, long-term dosing using smaller, fractionated doses was found to be more effective than larger, less frequent dosing. This is consistent with the clinical experience where IMMU-132 is administered on days 1 and 8 of a 21-day cycle, with cycles repeated for as long as possible. Some patients in the IMMU-132 Phase I/II trial have been under therapy for up to 11 months.
Immunomedics Inc. Reports IMMU-130 is Active in Patients with Irinotecan-Refractory Colorectal Cancer
Jun 2 14
Immunomedics Inc. reported 10 of 14 patients (71%) with metastatic colorectal cancer (mCRC) responded to IMMU-130, the Company's novel investigational antibody-drug conjugate (ADC) that comprises an anti-CEACAM5 antibody and SN-38, the active metabolite of irinotecan. A total of 21 patients with mCRC have been enrolled into the multicenter Phase I trial to receive IMMU-130 either once or twice weekly for 2 weeks in 3-week cycles. Treatment responses from 14 patients with at least one computed tomography (CT) assessment were presented at the 2014 Annual Meeting of the American Society of Clinical Oncology in Chicago, IL. The 14 CT-assessable patients had a median of 4.5 prior therapies (range 1 - 11), one of which must have been an irinotecan-containing regimen. Median time to progression for all 14 patients was at least 15.0 weeks (range 5.9 - >41.1 weeks), with 1 patient showing an 84% tumor shrinkage and an ongoing duration of partial response of more than 7 months. This patient continues to receive treatment and has received a total of 42 doses of the ADC thus far. However, to date, retreated patients have not shown an immune response to the ADC. The frequent dosing of IMMU-130 appears to be well tolerated by patients, with transient and reversible neutropenia, and manageable diarrhea the major side effects, which were mild and irregular.
Immunomedics, Inc. Reports Development of Improved Cancer Immunotherapy at the 2014 Annual Meeting of the American Society of Clinical Oncology
Jun 1 14
Immunomedics Inc. reported the development of bispecific antibodies that redirect human T-cells to certain solid cancers. T-cell redirected therapy of cancer is one of several new methods of cancer immunotherapy being studied both clinically and preclinically. In contrast to hematological tumors, little progress has been made in this approach to treat the more challenging solid cancers, including pancreatic and gastric cancers, two malignancies with very high rates of mortality. The company has previously reported the development of (E1)-3s, a novel investigational T-cell redirecting bispecific antibody created using the company's patented DOCK-AND-LOCK protein conjugation technology, for the potential treatment of pancreatic and gastric cancers. These and various other solid cancers express high-levels of TROP-2, a target recognized by the bispecific (E1)-3s, which also binds to the CD3 antigen on T cells. (E1)-3s has previously been shown to effectively induce a potent and specific T-cell-mediated killing of human pancreatic and gastric cancer cell lines. In the current study, the effect of interferon- (IFN-), which has demonstrated clinical efficacy in multiple solid cancers, on the T-cell redirecting bispecific antibody was evaluated using animal models of human pancreatic or gastric cancer. In the gastric cancer model, treatment with a combination of IFN- and (E1)-3s bispecific antibody was superior to the bispecific antibody alone (p=0.0007) in delaying the out-growth of tumor. The combination also significantly delayed tumor growth in the pancreatic cancer model compared to all other treatment groups (p<0.0007), including the IFN- only treatment group.