FDA Pipeline: Designations for Treatments of Graft-vs-Host-Disease, Colorectal Cancer, Pancreatic Cancer, and More


Key Points

  • The FDA’s Fast Track program is designed to facilitate the development of new treatments for serious or life-threatening conditions for which there is a significant unmet medical need. A therapeutic agent that receives Fast Track designation can benefit from early and frequent communication with the agency, in addition to a rolling submission of the marketing application, with the objective of getting important new therapies to patients more quickly.
  • Orphan Drug designation is granted to drugs and biologics that are intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. This designation provides certain incentives, such as tax credits toward the cost of clinical trials and prescription drug user fee waivers. If a product holding Orphan Drug designation receives the first FDA approval for the disease in which it has such designation, the product is entitled to 7 years of market exclusivity, which is independent from intellectual property protection.

The U.S. Food and Drug Administration (FDA) recently issued the following new designations and clearances:

Fast Track Designation for Itolizumab for the Treatment of Acute Graft-vs-Host Disease

The FDA granted Fast Track designation to itolizumab for the treatment of acute graft-vs-host disease. Itolizumab is a clinical-stage, first-in-class monoclonal antibody that selectively targets CD6, a novel immune checkpoint pathway. CD6 plays a central role in the modulation of Teff cell activity and trafficking. Activated Teff cells drive a number of immuno-inflammatory diseases across therapeutic areas

Initiation of a phase Ib/II clinical trial, called the EQUATE trial, is planned for early 2019. EQUATE will evaluate itolizumab in combination with corticosteroids for the initial treatment of patients presenting with acute graft-vs-host disease. The study will enroll approximately 84 patients to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of itolizumab.

The phase Ib component is an open-label dose-escalation trial. It will be followed by a phase II component, which is a randomized, double-blind, placebo-controlled trial in which subjects will receive either itolizumab or placebo in combination with corticosteroids over a 2-month period.

Fast Track Designation for GRANITE-001 in Colorectal Cancer

The FDA granted Fast Track designation to GRANITE-001 for the treatment of colorectal cancer.

GRANITE-001 is a personalized immunotherapy containing patient-specific neoantigens identified as the most relevant neoantigens to drive a tumor-specific T-cell attack. It is engineered to elicit a significant T-cell response (particularly CD8-positive cytotoxic T cells) against mutation-derived tumor-specific neoantigens identified for each patient through an artificial intelligence platform.

In combination with immune checkpoint blockade, GRANITE-001 is being evaluated in a phase I/II clinical study called GO-004 for the treatment of patients with common solid tumors, including metastatic non–small cell lung cancer, microsatellite-stable colorectal cancer, gastroesophageal cancer, and bladder cancer. The phase I study includes two parts: in part A, patients receive an adenovirus-based prime with escalating doses of an RNA-based boost vaccination in combination with anti–programmed cell death protein 1 (PD-1) therapy; in part B, patients receive the prime and the boost vaccinations at the selected dose in combination with both anti–PD-1 and anti–cytotoxic T-lymphocyte–associated protein 4 immunomodulatory antibodies.

Orphan Drug Designation for MB-102 for the Treatment of BPDCN

The FDA granted Orphan Drug designation to MB-102 (CD123 CAR T) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and incurable blood cancer with a median survival of less than 18 months and no standard of care.

MB-102 is a chimeric antigen receptor (CAR) T-cell therapy that is produced by engineering patient T cells to recognize and eliminate CD123-expressing tumors. CD123 is widely expressed on bone marrow cells of patients with myelodysplastic syndromes, as well as in hematologic malignancies including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, hairy cell leukemia, BPDCN, chronic myeloid leukemia, and Hodgkin lymphoma.

MB-102 is currently being studied in a single-center, first-in-human phase I dose-escalation clinical trial evaluating the safety and antitumor activity of escalating doses of MB-102 in patients with relapsed or refractory AML (cohort 1) and BPDCN (cohort 2). Patients receive a single dose of MB-102 with an option for a second infusion if they continue to meet safety and eligibility criteria and still have CD123-positive disease.

MB-102 has demonstrated complete responses at low doses in AML and BPDCN—without dose-limiting toxicities.

Orphan Drug Designation Granted for SM08502 for the Treatment of Pancreatic Cancer

The FDA granted Orphan Drug designation for SM08502 for the treatment of pancreatic cancer.

SM08502 is a small-molecule Wnt pathway inhibitor being developed for the treatment of advanced solid tumors. The mechanism of action of SM08502 has potential to attenuate the expression of genes that control differentiation and proliferation of tumor cells.

A phase I, open-label, multicenter, dose-escalation study is currently evaluating the safety, tolerability, and pharmacokinetics of orally administered SM08502 in subjects with advanced solid tumors.

Investigational New Drug Clearance for MCLA-145 in Solid Tumors

The FDA accepted an investigational new drug application for MCLA-145 for the treatment of solid tumors. 

Discovered through an unbiased functional screening of multiple immunomodulatory target combinations, MCLA-145 is a T-cell agonist that binds with high affinity and specificity to human programmed cell death ligand 1 and CD137 in preclinical models. The unique immunostimulatory profile of MCLA-145 derives from the ability to potently activate immune effector cells in the context of the tumor microenvironment, while simultaneously blocking inhibitory signals in the same immune cell population.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.