Merck 2014 Annual Report Download - page 75

70 GROUP MANAGEMENT REPORT → FUNDAMENTAL INFORMATION ABOUT THE GROUP → Research and development at the group
2014 ASCO Meeting. No significant improvement in progression-
free survival was observed and development therefore will not
continue in this indication.
BGB-290 (an inhibitor of poly [ADP-ribose] polymerase, or
PARP), currently being developed in collaboration with BeiGene,
entered PhaseI clinical testing in patients with solid tumors.
Enrollment was discontinued in a combination PhaseII study
of the MEK inhibitor pimasertib (a small-molecule inhibitor of
MEK, an enzyme that is a part of a pathway that is frequently
activated in many types of solid tumors) and the PI3K / mTOR in-
hibitor from Sanofi U.S. (SAR245409) in low- grade serous ovarian
cancer. This decision was based on the results of a futility analysis,
conducted by the
IDMC, which indicated that the trial was no
longer expected to achieve its objective of showing a meaningful
difference between the efficacy of the combination compared with
pimasertib alone. However, the safety profile was in line with pre-
vious clinical data for this combination, and no unusual toxicities
outside of those associated with this class were observed. The
further development of pimasertib in pancreatic cancer was also
discontinued as a PhaseII study in this indication did not reach its
primary endpoint of prolongation of progression-free survival.
Pimasertib will continue to be investigated in patients with
NRAS
mutant malignant melanoma in a PhaseII trial which is fully re-
cruited, and expected to report results on progression- free survival
(primary endpoint) during 2015. Additionally, a Phase Ib trial in
solid tumors, in collaboration with Sanofi U.S., investigating
pimasertib in combination with Sanofi U.S.’s hDM2 antagonist
(SAR405838) will also continue.
MSC 2490484A ( DNA -PK inhibitor), a small-molecule inhibitor
of the repair mechanisms of DNA damage in cancer cells, entered
PhaseI clinical testing in patients with solid tumors.
The Biopharmaceuticals division
and Sutro Biopharma, a pri-
vately held biotechnology
company, entered into a collaboration
and license agreement to develop next-generation antibody drug
conjugates (ADCs) for multiple targets in oncology. The Bio-
pharmaceuticals division and Mersana Therapeutics, Inc. also
announced a cooperation agreement to develop next- generation
ADCs. ADCs are composed of an antibody linked to a cytotoxic
drug, whereby the antibody part specifically targets and delivers
the cytotoxic drug to cancer cells, which could lead to higher drug
levels at the tumor site.
In October2014, the Biopharmaceuticals division, the Institute
of Cancer Research ( ICR ), London, and the Wellcome Trust, London,
entered into a co-development and license agreement building
on two independent research programs at both the ICR and the
Biopharmaceuticals division to identify inhibitors of tankyrase, an
enzyme of the poly (ADP- ribose) polymerase (PARP) family. In a
joint effort, this collaboration will aim to progress chemical com-
pounds that have emerged from both organizations’ tankyrase
inhibitor programs towards clinical development. At the end of
the collaboration period, the Biopharmaceuticals division will
take over full responsibility for the selected clinical development
candidate. The agreements mentioned above underline the Bio-
pharmaceuticals division’s approach to employing a collaborative
research and development model, creating strategic partnerships
in order to drive innovation.
Immuno-Oncology
For avelumab (also known as MSB0010718C), an investigational
anti-PD-L1 antibody currently in development, initial data from
the PhaseI dose escalation study in solid tumors were presented
at ASCO 2014. The study is advancing rapidly and anti-tumor
activity of avelumab has already been observed in a number of
patients, notably in NSCLC and in ovarian cancer. Avelumab is
also being tested in a Phase II study initiated in July 2014 in
patients with metastatic Merkel cell carcinoma. This is an aggres-
sive form of skin cancer, which is rare and currently has limited
treatment options. The study is a multicenter, single-arm, open
trial in patients who have previously been treated with one line of
chemotherapy.
In November2014, the Group announced that it had entered
into a global strategic alliance with Pfizer Inc. to develop and
commercialize avelumab in order to accelerate both companies’
presence in immuno-oncology. The antibody will be developed as
a single agent as well as in various combinations with Pfizer’s and
the Biopharmaceuticals division’s broad portfolio of approved and
investigational pipeline candidates. The two companies will also
combine resources and expertise to advance Pfizer’s anti-PD-1
antibody into PhaseI trials. As part of the strategic alliance, Merck
KGaA, Darmstadt, Germany, will co-promote Pfizer’s Xalkori®, a
medicine to treat NSCLC, in the United States and several other
key markets. Global collaboration with Pfizer is expected to accel-
erate the development of avelumab in multiple tumor types. Up to
20 high priority immuno-oncology clinical development programs
are expected to commence in 2015, including up to six pivotal
registration studies. The global alliance is expected to enable the
Group’s entry into the U.S. oncology market and to strengthen its
Oncology franchise in several other important global markets.