docetaxel nanoliposome (MM-310) / Merrimack - LARVOL DELTA

Novel co-delivery of oridonin and docetaxel nanoliposome for an enhanced antitumor effect on esophageal cancer. (PubMed, J Gene Med) - "The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer."

Journal • Esophageal Cancer • Gastrointestinal Cancer • Oncology

Patient Characteristics, Treatment and Long-term Outcomes from a Real-World Population of Early Breast Cancer Patients at High risk of Recurrence in Scotland (SG-BCC 2023) - "The monarchE randomized phase III clinical trial established benefit of combining adjuvant endocrine treatment (AET) with abemaciclib in 18th St.Gallen International Breast Cancer Conference / The Breast 62S1 (2023) S15–S136 S21 HR+, HER2− node positive EBC patients (pts) at high risk of recurrence. Overall, 1498 hRisk pts were identified (median age 59 years, female 99%, post-menopausal 71%). Baseline demographic differences compared to the monarchE trial may be attributed to clinical trial selection biases versus real-world population. More than half of all hRisk pts had a grade 3 tumour (>57%)."

Clinical • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Actively Targeted Nanomedicines in Breast Cancer: From Pre-Clinal Investigation to Clinic. (PubMed, Cancers (Basel)) - "Currently, there are 14 nanomedicines that have reached the clinic for the treatment of breast cancer, 4 of which are already approved (Kadcyla, Enhertu, Trodelvy, and Abraxane)...In TNBC these conjugates (Trodelvy, Glembatumumab-Vedotin, Ladiratuzumab-vedotin, Cofetuzumab-pelidotin, and PF-06647263) are directed against various targets, in particular Trop-2 glycoprotein, NMB glycoprotein, Zinc transporter LIV-1, and Ephrin receptor-4, to achieve this selective accumulation, and include campthotecins, calicheamins, or auristatins as drugs. Apart from the antibody-drug conjugates, there are other active targeted nanosystems that have reached the clinic for the treatment of these tumors such as Abraxane and Nab-rapamicyn (albumin nanoparticles entrapping placlitaxel and rapamycin respectively) and various liposomes (MM-302, C225-ILS-Dox, and MM-310) loaded with doxorubicin or docetaxel and coated with ligands targeted to Ephrin A2, EPGF, or HER-2 receptors. In this work,..."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

A phase 1 study evaluating the safety, pharmacology and preliminary activity of MM-310 in patients with solid tumors. (ASCO 2018) - P1; "MM-310 is an EphA2-targeting liposomal form of a docetaxel prodrug. Enrollment was initiated in March 2017. Five sites in the United States are open for enrollment."

Clinical • P1 data • Bladder Cancer • Endometrial Cancer • Gastric Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Triple Negative Breast Cancer

Targeting EphA2 in bladder cancer using a novel antibody-directed nanotherapeutic (AACR 2018) - "In the PDX models, MM-310 controlled tumor growth, mediated greater regression, and was more active than free docetaxel at equitoxic dosing (Table). Additionally, the combination of MM-310 and gemcitabine controlled tumor growth better than each drug alone, and outperformed the combination of free docetaxel and gemcitabine in the single PDX model where it was compared.Thus, in bladder cancer models, a docetaxel-based ADN as a monotherapy and in combination with gemcitabine targeted EphA2 and led to significant tumor regression.Maximum tumor regression (%) & Time to regrowth (days)Model Name Control Docetaxel MM-310 p valueBL0293 -2% & 3 days -58% & 55 days -100% & 120 days <.05 & <.001BL0382 0% & 3 days -16% & 34 days -100% & 106 days <.001 & <.001BL0440 0% & 7 days -43% & 41 days -84% & 67 days <.01 & <.01BL417362 0% & 5 days -47% & 69 days -100% & 121 days <.05 &a

IO Biomarker • Bladder Cancer

Engineering and development of novel antibody-directed nanotherapeutics for the treatment of cancer (ACS-Fall 2018) - "Here we demonstrate the potential of this platform through the engineering of an EphA2- antibody targeted nanotherapeutic encapsulating a novel docetaxel prodrug (MM-310). The sustained tumor exposure results in a significant increase in antitumor activity in multiple xenograft tumor models compared to free docetaxel, and the ability to be more readily combined with a range of combination partners. Finally, we describe the use of nano-sized imaging agents to predict the distribution and activity of both targeted and non-targeted nanotherapeutics."

Biosimilar • Oncology

Merrimack to present at the 2017 American Association for Cancer Research Annual Meeting (Merrimack Press Release) - "Presentations to include data on MM-310, a novel antibody-directed nanotherapeutic targeting EphA2, and istiratumab (MM-141)...Also highlighted at the conference will be preclinical data for MM-141 (istiratumab), a monoclonal bispecific antibody that acts as a tetravalent inhibitor of IGF1-R and HER3, and MM-161, a novel first-in-class pan-FGFR antibody."

Clinical data • Conference • Preclinical • Oncology

A Study Evaluating MM-310 in Patients With Solid Tumors (clinicaltrials.gov) - P1; N=34; Recruiting; Sponsor: Merrimack Pharmaceuticals; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Bladder Cancer • Breast Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Triple Negative Breast Cancer • Uterine Cancer

A Study Evaluating MM-310 in Patients With Solid Tumors (clinicaltrials.gov) - P1; N=34; Not yet recruiting; Sponsor: Merrimack Pharmaceuticals

New P1 trial • Biosimilar • Bladder Cancer • Breast Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Triple Negative Breast Cancer • Uterine Cancer

Merrimack reports third quarter 2018 financial results and provides strategic update following portfolio review (PRNewswire) - P1, N=34; NCT03076372; Sponsor: Merrimack Pharmaceuticals; P2, N=80; SHERBOC (NCT03241810); Sponsor: Merrimack Pharmaceuticals; "'...we are now focused on our clinical development program for MM-310, for which we anticipate providing another safety update in Q1 2019, and our emerging preclinical candidates, MM-401 and MM-201.'...Merrimack is discontinuing development of all ongoing MM-121 programs, including terminating the SHERBOC study, its companion Phase 2 clinical trial evaluating MM-121 in metastatic breast cancer."

P1 data • Preclinical • Trial termination • Breast Cancer • Oncology • Solid Tumor

"$MACK lowers headcount to 13 following discontinuation of MM-310 development https://t.co/E2tIrlooPF" (@BioStocks)

"Weird. Isn't MM-310 an Ipsen asset now, along with the rest of the $MACK oncology portfolio?" (@JacobPlieth)

Merrimack discontinues development of MM-310 (PRNewswire) - "Merrimack Pharmaceuticals...announced the Company is discontinuing development of MM-310, its antibody-directed nanotherapeutic for the treatment of solid tumors. This decision was the result of a comprehensive review of available safety data from its Phase 1 study. Based on emerging data since the recent amendment of the clinical protocol, the Company has concluded that the study would not be able to reach an optimal therapeutic index for MM-310."

Discontinuation