Market Overview

Merrimack Pharmaceuticals Presents Phase 1 Clinical Data Supporting Four Novel Antibody Therapeutic Programs at the 2014 ASCO Annual Meeting

Merrimack Pharmaceuticals Presents Phase 1 Clinical Data Supporting Four
Novel Antibody Therapeutic Programs at the 2014 ASCO Annual Meeting
Planning Underway for Phase 2 Studies for MM-151 in Colorectal Cancer and
MM-141 in Front Line Pancreatic Cancer
CHICAGO, June 2, 2014 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc.
(Nasdaq: MACK) today announced that Phase 1 clinical data from studies of
MM-151, MM-141, MM-111 and MM-121 was presented at the 2014 American Society
of Cancer Oncology (ASCO) Annual Meeting. Data from these studies support
the clinical advancement of Merrimack's novel antibody therapeutics.
"We are excited to announce Phase 1 results for MM-151 and MM-141 - two
antibody therapeutics engineered with insights from our systems biology
approach. This progress continues to support our goal of transforming cancer
care by developing therapeutics that target key pathways responsible for
tumor growth and survival. We look forward to initiating biomarker-directed
Phase 2 studies with MM-151 and MM-141," said Ulrik Nielsen, Ph.D.,
Co-Founder and Chief Scientific Officer at Merrimack.
-- Preliminary results from a Phase 1 study of MM-151, a novel oligoclonal
anti-EGFR antibody combination, in patients with refractory solid tumors

suggested clinical activity in colorectal cancer with an acceptable
safety profile consistent with EGFR inhibition. Planning is underway for

a Phase 2 study testing MM-151 in colorectal cancer.

-- Merrimack's MM-141, a tetravalent bispecific antibody designed to block
tumor survival signals by targeting receptor complexes containing IGF-1R

and ErbB3, has completed the monotherapy arm in a Phase 1 study and
reports no dose-limiting toxicities. The next step for MM-141 is
anticipated to be a Phase 2 study testing MM-141 in front line
pancreatic
cancer.

-- Merrimack also presented a Phase 1 multi-arm study of MM-111 in
combination with standard of care regimens in multiple tumor types as
well as a Phase 1 study of MM-121 in combination with cetuximab and
irinotecan in patients with advanced solid cancers.
To access clinical posters presented at ASCO 2014, click here.
Methodology and Results:
Preliminary Results from a Phase 1 Trial of MM-151 in Patients with
Refractory Solid Tumors
MM-151 is a novel oligoclonal anti-EGFR antibody combination designed to
target EGFR-driven tumor growth. Preliminary data from a Phase 1 study in
patients with refractory solid tumors show that MM-151 has an acceptable
safety profile and preliminary signs of clinical activity in colorectal
cancer.
-- A total of 69 patients have been enrolled at escalating dose levels,
with
the most common tumor types including colorectal cancer (28 [41%]),
non-small cell lung cancer (9 [13%]), head and neck cancers (5 [7%]),
and
pancreatic cancer (6 [9%]).

-- The most common adverse event seen thus far was infusion related
reaction
(47 [68.1%]), which was managed with premedication and an optimized
infusion schedule.

-- Partial responses (PR) were observed in two colorectal cancer patients
and a total of eight (29% of mCRC) patients had stable disease (SD) for
greater than four months.

-- Planning is underway for a Phase 2 trial to evaluate MM-151 in
colorectal
cancer.
Results from the Completed Monotherapy Arm of a Phase 1 Study of MM-141 in
Patients with Advanced Solid Tumors
A Phase 1 dose-escalation study in patients with advanced solid tumors
tested the tolerability and safety of MM-141, a novel tetravalent bispecific
antibody inhibitor which targets both IGF-1R and ErbB3. MM-141 blocks and
degrades complexes containing IGF-1R and ErbB3 receptors, leading to the
downstream inhibition of tumor pro-survival signaling. Preclinical studies
have shown that MM-141 has higher activity compared to a mixture of separate
anti-IGF-1R and ErbB3 antibodies.
-- This clinical study enrolled three arms: MM-141 as a monotherapy, MM-141

in combination with everolimus and MM-141 in combination with
nab-paclitaxel and gemcitabine. Data presented at the 2014 ASCO Annual
Meeting detailed the completion of the monotherapy arm.

-- There were no dose-limiting toxicities observed in the monotherapy arm
at
any dose level. The most common adverse events that were not deemed
related to MM-141 monotherapy were vomiting, nausea, fatigue, abdominal
pain and dyspnea.

-- MM-141 monotherapy showed preliminary activity with disease
stabilization
observed in patients with Ewing's Sarcoma and parotid gland carcinoma.

-- Planning is underway for a Phase 2 study of MM-141 in combination with
nab-paclitaxel and gemcitabine in front line pancreatic cancer.
Results from a Phase 1, multi-arm study of MM-111 in combination with
standard of care regimens in multiple tumor types
MM-111 is a bispecific antibody designed to inhibit HER3 (ErbB3) signaling
in HER2-positive tumors. Preclinical research has shown that MM-111 restores
sensitivity to chemotherapy and HER2-targeted treatment. MM-111 was tested
in a Phase 1 study in combination with a variety of standard of care
HER2-targeted regimens, namely: 1) capecitabine, cisplatin and trastuzumab;
2) lapatinib with or without trastuzumab; 3) paclitaxel and trastuzumab; 4)
lapatinib, paclitaxel and trastuzumab; and 5) docetaxel and trastuzumab. The
study enrolled patients with multiple HER2 positive tumor types, including
breast, bladder, colorectal, gastric, esophageal and ovarian cancers. Each
arm in the study was designed to run as a separate Phase 1 trial to address
safety and tolerability of MM-111, and utilized a "3+3" design with standard
dosing of the standard of care regimen.
-- A total of 86 patients with advanced HER2+ cancers were enrolled in the
study.

-- The combination of MM-111 with standard HER2-directed therapy was
generally feasible with standard doses for the HER2 directed therapies.
Only Arm 1 required a reduction in the dose of capecitabine to 800 mg/m2

as a result of dose limiting toxicity.

-- Adverse events reported for MM-111 in combination with the standard of
care HER2-targeted regimens were similar to adverse events reported for
the regimens alone, which included diarrhea, fatigue, decreased
appetite,
neutropenia and hypokalaemia.

-- Across all dosing regimens, the overall clinical benefit rate, defined
as
complete response, PR and SD for at least four months, was 55% in 86
evaluable patients.

-- The combination of MM-111 and standard of care HER2 directed regimens
showed clinical activity across a variety of advanced solid tumors with
objective responses being observed in multiple HER2-positive tumor
types.

-- MM-111 is currently in a biomarker stratified Phase 2 study testing
MM-111 in combination with trastuzumab and paclitaxel in patients with
advanced gastric, esophageal and gastroesophageal junction cancers.
Results from a Phase 1 Study of MM-121 in Combination with Cetuximab and
Irinotecan in Patients with Advanced Cancers
This Phase 1 trial assessed the safety, tolerability and pharmacokinetic
properties of MM-121 in combination with cetuximab or with cetuximab and
irinotecan in patients with advanced solid cancers. MM-121 is a fully human
monoclonal antibody that targets ErbB3, a cell surface receptor that is
activated by the ligand heregulin.
-- Patients were dosed in a standard "3+3" design with escalating doses of
MM-121 and cetuximab in two groups without (n=34) or with biweekly
irinotecan (n=14).

-- The most common adverse events from across the entire study included
fatigue, hypomagnesemia, diarrhea and hypokalemia.

-- Across all dosing regimens, 18/48 (37.5%) of patients achieved a best
overall response of SD or PR, 14/48 (29.2%) had SD, 4/48 (8.3%) had a
PR.
Of the four patients who had PR, two had KRAS wild-type colorectal
cancer,
one had cholangiocarcinoma and one had NSCLC.

-- One colorectal cancer patient previously treated with cetuximab and
irinotecan achieved a PR on the MM-121/cetuximab/irinotecan combination.

One head and neck cancer patient who previously received cetuximab
achieved a durable response of SD on the MM-121/cetuximab combination.

-- Phase 2 doses were established for the combination of MM-121 and
cetuximab and MM-121, cetuximab and irinotecan.

Posted-In: News FDA Press Releases

 

Related Articles (MACK)

Around the Web, We're Loving...

Get Benzinga's Newsletters