Program Status
Active, not recruitingPhase
Phase 1Prior Immunotherapy Allowed
NoCRC-directed Trial
NoDrugs
5-FU + Cisplatin, Evorpacept (ALX148), Pembrolizumab, Ramucirumab + Paclitaxel, Rituximab, TrastuzumabTags
MSS/ MMRpComments
Phase 1 protocol will have 2 parts: a single agent dose escalation phase (Part 1) and a combination therapy phase (Part 2), with Pembrolizumab, Trastuzumab, or Rituximab .
Part 2 will include an initial dose escalation portion followed by a dose expansion portion.
CD47/SIRPa-blocking agent ALX148
Potential phagocytosis-inducing, immunostimulating and antineoplastic activities. Upon administration, ALX148 binds to CD47 expressed on tumor cells and prevents the interaction of CD47 with its ligand SIRPa, a protein expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of the pro-phagocytic signaling protein calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages. This results in macrophage activation and the specific phagocytosis of tumor cells. In addition, blocking CD47 signaling activates both an anti-tumor cytotoxic T-lymphocyte (CTL) immune response and T-cell-mediated killing of CD47-expressing tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate.
| Location | Location Status |
|---|---|
| United States | |
|
University of Colorado Denver Denver, Colorado 80045 |
Active, not recruiting |
|
Yale University New Haven, Connecticut 06520 |
Active, not recruiting |
|
Massachusetts General Hospital Boston, Massachusetts 02114 |
Active, not recruiting |
|
Dana Farber Cancer Institute Boston, Massachusetts 02215 |
Active, not recruiting |
|
START-Midwest Grand Rapids, Michigan 49503 |
Active, not recruiting |
|
Seattle Cancer Care Alliance Seattle, Washington 98109 |
Active, not recruiting |
| Korea, Republic of | |
|
Seoul National University Bundang Hospital Seongnam |
Active, not recruiting |
|
Samsung Medical Center Seoul |
Active, not recruiting |
|
Seoul National University Hospital Seoul |
Active, not recruiting |
|
Severance Hospital, Yonsei University Seoul |
Active, not recruiting |
Inclusion Criteria
Inclusion Criteria:
Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy; or relapsed or refractory Non-Hodgkin lymphoma for whom no standard therapy is available..
Adequate Bone Marrow Function.
Adequate Renal & Liver Function.
Adequate Performance Status
Exclusion Criteria
Exclusion Criteria:
Patients with known symptomatic CNS metastases or lepotomeningeal disease requiring steroids.
Previous high-dose chemotherapy requiring allogenic stem cell rescue.
Prior treatment with a CD47 or signal regulatory protein (SIRP) alpha targeting agent.
