MM-151 / Merrimack - LARVOL DELTA

Characterization of egfr ectodomain mutation in acquired resistance to cetuximab in colorectal cancer (AACR 2025) - "Using 2D and 3D drug sensitivity assays, we demonstrate that this EGFR ectodomain mutation, in addition to being resistant to cetuximab and panitumumab, also could not be targeted by the oligoclonal anti-EGFR antibody cocktail MM-151. Further, our structural, functional, and biochemical studies implicate reduced binding of EGFR mutant to cetuximab and sustained downstream signaling activity as a cause of cetuximab resistance. Collectively, this mutation necessitates additional treatment strategies for a subset of subjects with advanced CRC who do not respond to treatment with current anti-EGFR biologics."

Preclinical • Colorectal Cancer • Oncology • Solid Tumor • BRAF • EGFR • KRAS • NRAS

Characterization of EGFR ectodomain mutation in acquired resistance to cetuximab in colorectal cancer (AACR 2024) - "Further structural, and functional characterization is underway for this ectodomain mutation that confers resistance to cetuximab and will be shared during the meeting. These findings necessitate the need for additional treatment strategies for a subset of subjects with mCRC who do not respond to treatment with cetuximab/panitumumab and MM-151."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • KRAS • NRAS • RAS

Identification and Characterization of Unique Neutralizing Antibodies to Mouse EGF Receptor. (PubMed, Gastroenterology) - No abstract available

Journal • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase 1 Combination Study of MM-151 With MM-121, MM-141, or Trametinib (clinicaltrials.gov) - P1; N=5; Terminated; Sponsor: Merrimack Pharmaceuticals; N=32 ➔ 5; Recruiting ➔ Terminated; Sponsor decision

Enrollment change • Trial termination • Biosimilar • Colorectal Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer

Merrimack Pharmaceuticals reports second quarter 2015 financial results (PRNewswire) - "Merrimack anticipates the following milestones in 2015: [1] Initiation of a clinical trial of MM-151 in EGFR-positive colorectal cancer; [2] Continued enrollment in HERMIONE, a Phase 2 clinical trial...[of] MM-302 in patients with HER2-positive metastatic breast cancer; [3] Continued enrollment in a Phase 2 clinical trial of MM-121 in patients with [mNSCLC]; and
[4] Continued enrollment in a Phase 2 clinical trial of MM-141 in patients with front-line metastatic pancreatic cancer...."

Anticipated enrollment status • Anticipated new trial • Breast Cancer • Colorectal Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer

Merrimack Pharma: Cantor Fitzgerald Healthcare Conference (Merrimack) - Anticipated launch of registration path studies in colorectal cancer in H2 2015

Anticipated new trial • Oncology

Merrimack and Baxalta announce initiation of phase 1 study of MM-151 in combination with the Onivyde (irinotecan liposome injection) regimen in metastatic colorectal cancer (Merrimack Press Release) - P1, N=NA; "Merrimack Pharmaceuticals, Inc...and Baxalta Incorporated...today jointly announced the initiation of a Phase 1 clinical study of Merrimack's oligoclonal EGFR (epidermal growth factor receptor) inhibitor, MM-151, in combination with ONIVYDE (irinotecan liposome injection) plus fluorouracil (5-FU) and leucovorin in patients with RAS wild-type metastatic colorectal cancer...The initiation of this study advances the development path for ONIVYDE."

Enrollment open • Trial initiation date • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Merrimack Pharma: ASCO 2016 (Merrimack) - "MM-151 has demonstrated a comparable safety profile to approved EGFR inhibitors as a monotherapy and in combination with irinotecan"; "Dosing schedule was established, including priming doses and premedication, followed by weight-based dosing at a staged rate increase"; "Clinical validation of MM-151 mechanistic foundations observed in EGFR downregulation, expression of high affinity ligands across indications (including refractory mCRC) and activity in tumors expressing EGFR and downstream mutations (acquired and de novo)"; "Decrease in measurable lesions observed in 54% of evaluable patients in CRC cohort were observed in both WT and mutant patients"; "MM-151 demonstrates promising activity in highly refractory patient populations. Additional studies are planned within mCRC and other EGFR-driven indications as a monotherapy or in combination"

P1 data • Oncology

Merrimack Pharma: Annual Report 2014 (Merrimack) - Anticipated patent expiry for composition of matter in US and ex-US in 2031 and 2032; Anticipated patent expiry for methods of use in US and ex-US in 2031 and 2032; Anticipated patent expiry for diagnostics in US, EU and ROW in 2032; Anticipated patent expiry for dosage and administration in 2035

Anticipated patent expiry • Oncology

Merrimack Pharma: Analyst Day (ASCO 2016) - Anticipated launch of P1 trial of MM-151 in combination with Onivyde in 1st or 2nd line mCRC RAS wild type in Q2 2016

Anticipated new P1 trial • Colorectal Cancer • Oncology

MM151: Anticipated expiry of patents in US, Europe, Japan, ROW covering composition and related patient diagnostic technology in 2032 (Merrimack) - Annual Report 2016: Anticipated expiry of patents in US, Europe, Japan, ROW covering methods of treating colorectal cancer in 2035

Anticipated patent expiry • Oncology

Final results of a first-in-human study evaluating the safety, pharmacology and initial efficacy of MM-151, an oligoclonal anti-EGFR antibody in patients with refractory solid tumors (ASCO 2016) - P1, N=111; NCT01520389; Sponsor: Merrimack Pharmaceuticals; "Notably, clinically meaningful durations were achieved in patients presenting with multiple resistance markers, including RAS/RAF mutations. Within a CRC subset, 13/29 (45%) achieved SD or PR at 3 cycles of treatment and 5/29 (17%) achieved a PR, with highly durable responses and disease control."

P1 data • Colorectal Cancer • Non Small Cell Lung Cancer • Oncology

Merrimack: Credit Suisse Antibody Day 2015 (Merrimack) - “Safety: Safety is consistent with expected EGFR and irinotecan toxicities”; “Efficacy: Prolonged responses up to 87 weeks, Stable disease > 4 months in 9/27 CRC patients, Partial responses in 7 patients (5/7 are CRC)”

P1 data • Colorectal Cancer • Oncology

Evaluation of MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: Merrimack Pharmaceuticals; N=28 ➔ 0; Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Merrimack: ASCO GI 2015 (Merrimack) - “MM-151 administered on a QW schedule demonstrated objective clinical activity at dose levels > 6 mg/kg with an acceptable safety profile and exposure levels in the expected therapeutic range. Initial results with MM-151 monotherapy on a Q2W schedule and in combination with irinotecan were similarly encouraging”; “An RP2D of 10.5mg/kg was defined for the QW monotherapy schedule and an expansion cohort in cetuximab-refractory CRC has been initiated. MM-151 dose escalation continues on the Q2W-mono and irinotecan combination schedules”; “Prolonged stable disease and radiographic responses (3 monotherapy and 3 combination therapy partial responses) were observed in heavily pre-treated solid tumor patients, including those with prior cetuximab therapy. Initial biomarker data suggests particular clinical benefit in triple-wildtype, EGFR-ligand positive CRC patients”

P1 data • Colorectal Cancer • Oncology

Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models. (PubMed, J Exp Clin Cancer Res) - "These results suggest that combined therapy with MEK and PI3KCA inhibitors could represent a novel and effective treatment option for HER2-amplified colorectal cancer."

Journal • Preclinical