Date: 2016-05-19
Type of information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: Merrimack Pharmaceuticals (USA - MA)
Product: combination regimens including MM-151, istiratumab (MM-141), seribantumab (MM-121) selected using a combination of genetic and nongenetic biomarkers
Action
mechanism: monoclonal antibody/bispecific antibody. MM-151 is an oligoclonal therapeutic mixture consisting of three fully-human monoclonal antibodies designed to bind and inhibit signaling of the epidermal growth factor receptor (EGFR). EGFR-mediated signaling promotes the growth and survival of cancer cells and has long been recognized as an important drug target in several types of cancer, including colon, lung, breast, pancreatic, and head and neck cancers. MM-151 has previously been tested in a Phase 1 dose-escalation clinical trial in patients with advanced solid tumors.
Istiratumab (MM-141) is a tetravalent bispecific antibody designed to block tumor survival signals by inhibiting IGF-1R and ErbB3 (HER3) signaling. IGF-1R and ErbB3 complexes activate major signaling pathways that allow tumor cells to grow and develop resistance to chemotherapy. Currently, istiratumab is in Phase 2 testing in patients with metastatic pancreatic cancer that have a pre-defined IGF-1 biomarker profile. The FDA has granted orphan drug designation for istiratumab for the treatment of pancreatic cancer.
Seribantumab (MM-121) is Merrimack's wholly owned, fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner. Seribantumab has been investigated in multiple Phase 2 and Phase 1 clinical trials covering a broad spectrum of patient populations and drug combinations.
Disease: colorectal cancer, non-small cell lung cancer, squamous cell carcinoma of the head and neck
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This phase 1 study is an open-label, dose-escalation trial using "3+3" design, evaluating MM-151 co-administration with MM-121 at varying dose levels. (NCT02538627)
Latest
news: * On May 19, 2016, Merrimack Pharmaceuticals announced the initiation of a biomarker-selected, multi-arm Phase 1 clinical study in metastatic colorectal, non-small cell lung, and head and neck cancers. Merrimack's first-of-its-kind basket study will use a combination of genetic and nongenetic biomarkers to match patients to appropriate novel combinations of investigational drug regimens based on their cancer's molecular signature. This approach is expected to enable more than 95 percent of eligible patients to qualify for enrollment to one of the investigational arms of the study. All patients enrolling in the study will provide a core needle biopsy, which will be tested for KRAS and NRAS mutations and for expression of two resistance ligands - heregulin (HRG) and insulin-like growth factor 1 (IGF-1). Patients will receive Merrimack's oligoclonal EGFR (epidermal growth factor receptor) inhibitor, MM-151, in combination with another agent that is intended to target their cancer's mechanism of resistance to EGFR inhibition. Assignment to one of the four trial arms will be based on the following criteria:
Patients that test positive for HRG will be assigned to Group A and receive MM-151 in combination with seribantumab (MM-121), a fully human antibody designed to block heregulin-driven ErbB3 pro-survival signaling.
Patients that test negative for HRG and positive for activating mutations in either KRAS or NRAS will be assigned to Group B and receive MM-151 in combination with trametinib, a MEK inhibitor (Novartis). This regimen is designed to block signaling both upstream and downstream of RAS mutations.
Patients that test negative for HRG, wild-type for KRAS and NRAS, and positive for IGF-1 will be assigned to Group C and receive MM-151 in combination with istiratumab (MM-141), a bispecific antibody designed to block IGF-1R and ErbB3 pro-survival signaling.
Patients that test negative for both HRG and IGF-1 and wild-type for KRAS and NRAS will be assigned to Group D and receive MM-151 in combination with trametinib. This regimen is designed to block signaling from alternative receptors and to delay potential acquisition of KRAS and NRAS mutations.
