February 2014 | Volume 13 | Issue 2 | Features | 217 | Copyright © February 2014
Pipeline Previews brings to you information on the newest drugs and medical products as they become available to the dermatologic community. This department
may include additional information from the manufacturers, plus reports from physicians who wish to share their clinical experience with these new products. In
addition, we will inform our readers about the latest drugs receiving Food and Drug Administration (FDA) approval.
Agenus and Cancer Vaccine for Melanoma
Agenus Inc, a biotechnology company developing novel
immune system activating treatments for cancers and infectious
diseases, has announced initiation of a randomized
Phase 2 trial with Prophage for melanoma, and Bristol-Myers
Squibb's Yervoy® (ipilimumab) for the treatment of Stage III
and IV metastatic melanoma. The combination has the potential
to trigger a more effective immune response against
the tumor than Yervoy alone.
The Phase 2, randomized, open label, single-center, investigator-
sponsored trial is designed to evaluate the safety, feasibility
and immunogenicity of the combination of Prophage vaccine
and Yervoy with or without low dose cyclophosphamide (a
chemotherapy agent used in this study as an immunomodulator
of regulatory cells) in 25 patients with unresectable Stage
III or IV metastatic melanoma. The trial will be conducted at
the University of Texas Health Science Center at Houston and
led by clinical investigator Jorge Quesada MD.
Agenus’ Prophage Series vaccines are tailor-made for each patient
by processing tumor removed from the patient. Malignant cells
express proteins, which can be recognized as non-self by the
immune system. This recognition by T-lymphocytes can trigger
the immune system to attack the cancerous tissue, and under
favorable circumstances help the patient fight the cancer. Because
each patient’s cancer cells contains their own set of genetic
changes, the best chance to mount an effective immune attack on
the cancer resides in stimulating the immune response to the abnormal
proteins expressed in that patient’s cancer. Agenus’ heat
shock protein vaccines are processed by the company and then
re-introduced into the patient as a vaccine which is intended to
stimulate a targeted immune attack on their cancer cells.
Prophage Series vaccines are based on Agenus’ heat shock
protein platform technology. Prophage Series G-100 and G-200
vaccines are currently in Phase 2 programs for the treatment
of newly diagnosed and recurrent glioblastoma multiforme.
Merck and MK-3475
Merck has started a rolling submission to the FDA of a Biologics
License Application for MK-3475, the company’s investigational anti-PD-1 immunotherapy, for patients with
advanced melanoma who have been previously treated with
ipilimumab. A rolling submission allows completed portions
of the application to be submitted and reviewed by the FDA
on an ongoing basis. The company expects to complete the
application in the first half of 2014.
MK-3475 is currently being studied in three clinical trials for
advanced melanoma including a Phase III trial of MK-3475
versus ipilimumab in ipilimumab-naïve advanced melanoma
patients. Enrollment is complete in the advanced melanoma
cohorts in the company’s Phase IB trial and the Phase II trial
comparing two doses of MK-3475 versus chemotherapy in patients
with advanced melanoma who have progressed after
prior therapy. In April 2013, Merck announced that MK-3475
received a Breakthrough Therapy designation for advanced
melanoma from the FDA.
Intralesional Bevacizumab and Locally Advanced
Basal Cell Carcinoma
A study published in The Journal of European Academy of Dermatology
and Venereology, and authored by G. Gaitanis, and I.D.
Bassukas, seeks to report on the feasibility and effectiveness
of intralesional bevacizumab, an anti-VEGF antibody,
as an in-add adjuvant to immunocryosurgery (cryosurgery
sessions during daily topical imiquimod application) for the
treatment of locally advanced basal cell carcinoma.
Seven patients (six uncontrollable or extensive local disease;
one tumour unresponsive to repeated immunocryosurgery)
were treated with 1–3 sessions of intralesional injections of
bevacizumab (25 mg) at the day of cryosurgery during ongoing
immunocryosurgery. Follow-up after treatment was
In 4 of the 7 cases tumours cleared completely and 3 out of 7
remained relapse free during follow-up. A relapsed tumour and
a further case that did not clear after repeated immunocryosurgery
cycles were excised with significantly reduced burden
of surgery. Finally, two cases with previously locally uncontrollable
BCC tumours regressed significantly and stabilized.