MM-302 / Merrimack - LARVOL DELTA

Assessment of safety and activity in an expanded phase 1 study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced HER2-positive (HER2+) breast cancer (SABCS-2013) - Abstract #P4-12-29; P1, N=27; "At the time of this analysis (n=27), overall response rate was 17% (4 out of 24 evaluable patients) and the estimated median Progression Free Survival (PFS) was 5.7 months, with six patients still receiving treatment. Eight patients (30%) had a PFS of greater than 6.0 months. Neutropenia was the most common treatment-related grade 3/4 toxicity and occurred in 15% of patients. The most common adverse events include fatigue, nausea, vomiting, and decreased appetite."

P1 data • Breast Cancer • Oncology

Antibody-Drug Conjugates in Breast Cancer: a Comprehensive Review. (PubMed, Curr Treat Options Oncol) - "In breast cancer, the early success of trastuzumab-emtansine (T-DM1) in the HER2-positive metastatic setting led to great hopes, later dashed by results in the early setting (KRISTINE trial) and in combination with pertuzumab (MARIANNE trial). Parallel to this, development of ADCs in breast cancer has suffered other setbacks, including the recent failure of other agents (MM-302) as well as the suspension of a few programs (XMT-1522, ADCT-502) with the overall effect of dampening the impetus of this concept and halting/delaying the progress of drugs associated with it, particularly when immunotherapy is at the center of so many efforts...Finally, breakthroughs are occurring in the orphan triple-negative breast cancer subtype with agents targeting surface proteins. The recent results of Sacituzumab govitecan suggest substantial activity in heavily pre-treated patients and underscore the enduring relevance of antibody drug conjugates as a path towards better outcomes."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Triple Negative Breast 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

Safety and Pharmacokinetic Study of MM-302 in Patients With Advanced Breast Cancer (clinicaltrials.gov) - P1; N=75; Active, not recruiting; Sponsor: Merrimack Pharmaceuticals; Trial primary completion date: Nov 2015 ➔ May 2016

Trial primary completion date • Biosimilar • Breast Cancer • Oncology • Triple Negative Breast Cancer

Merrimack Pharmaceuticals presents research on innovative pipeline for patients with breast cancer at the 2014 San Antonio Breast Cancer Symposium (Merrimack Press Release) - "Merrimack Pharmaceuticals...announced data from multiple presentations at the 2014 San Antonio Breast Cancer Symposium in San Antonio, TX. Presentations include preclinical research and clinical data on MM-398, MM-302 and MM-121."

Clinical data • Conference • Preclinical • Breast Cancer • Oncology

Q2 2012 Results (Merrimack) - Anticipated presentation of data from P1 monotherapy study for breast cancer by August 2013

Anticipated P1 data • Breast Cancer

A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2- positive breast cancer (SABCS 2012) - P1, N=14; “...The most frequent AEs were constipation (53.8%), Fatigue (69.2%) and decreased appetite (46.2%). Five patients have achieved SD and one patient has achieved a PR. A pharmacokinetic analysis indicates a half-life of approximately 50 hours...”

P1 data • Breast Cancer • Oncology

Merrimack announces encouraging clinical data from expanded phase 1 study of MM-302 for the treatment of advanced HER2-positive breast cancer (Merrimack Press Release) - P1, N=47; NCT01304797; Sponsor: Merrimack; "The most common adverse events were fatigue, nausea and decreased appetite....patients treated with MM-302 as a monotherapy at doses of 30, 40 and 50 mg/m2 had an estimated progression free survival (PFS) of 5.6 months (95% CI: 2.8-10.9 months) and a clinical benefit response rate of 37%....5 of 9 patients who had not been previously treated with anthracyclines had a PFS of greater than 9 months....A Phase 2 study for MM-302 is being planned in patients with HER2-positive breast cancer."

Anticipated new P2 trial • P1 data • Breast Cancer • Oncology

Merrimack Pharmaceuticals to present phase 1 data on MM-302 in patients with advanced HER2-positive breast cancer (Merrimack Press Release) - P1, N=75; NCT01304797; Sponsor: Merrimack; "Merrimack Pharmaceuticals...announced that Phase 1 data evaluating safety of the novel agent MM-302 in patients with advanced HER2-positive breast cancer will be presented at the 2013 San Antonio Breast Cancer Symposium (SABCS), December 10-14, 2013 in San Antonio, Texas....Data to be presented will include safety results for all treated patients in the trial, as well as preliminary activity in patients treated with therapeutically relevant dose levels of MM-302 alone and in combination with trastuzumab."

Anticipated conference • Anticipated P1 data • Breast Cancer • Oncology

Instrumental improvements for the trace analysis of structural isomers of polycyclic aromatic hydrocarbons with molecular mass 302 Da. (PubMed, Anal Chim Acta) - "The research presented here focuses on the analysis of PAH isomers of MM 302 Da...This feature, associated to unique vibrational fluorescence profiles and lifetime decays, allows for the unambiguous identification of co-eluting isomers in RPLC fractions. The same is true for their quantitative analysis in coal tar samples."

Journal

Nanoliposome targeting in breast Cancer is influenced by the tumor microenvironment. (PubMed, Nanomedicine) - "MM-302 is an anti-HER2 antibody-targeted pegylated liposomal doxorubicin designed to deliver doxorubicin specifically to HER2-expressing solid tumors. The effect of HER2-targeting was greatest in the lung where lymphatic vessel density and MM-302 delivery were highest. Our data indicate that the therapeutic advantage of actively targeting a nanoliposome with an antibody is influenced by both target expression and the tumor microenvironment."

Biomarker • Journal • Tumor microenvironment

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody-liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study. (PubMed, Br J Cancer) - "MM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m plus 6 mg/kg trastuzumab q3w."

Clinical • Journal • P1 data • PK/PD data