CC-90002 / Inhibrx Biosci, BMS - LARVOL DELTA

Effects of a humanized CD47 antibody and recombinant SIRPα proteins on triple negative breast carcinoma stem cells. (PubMed, Front Cell Dev Biol) - "This indicates that SIRPα-Fc has CD47-mediated agonist activities in breast cancer stem cells affecting proliferation and metastasis pathways that differ from those of CC-90002. This SIRPα-induced CD47 signaling in breast carcinoma cells may limit the efficacy of SIRPα decoy therapeutics intended to stimulate innate antitumor immune responses."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALDH1A1 • CD47 • SIRPA

CC-90002 (anti-CD47 antibody) in vivo anti-tumor activity is associated with an increase in M1-polarized macrophages (AACR 2017) - P1; "This would presumably shift the overall balance of tumor-associated macrophages toward the M1 phenotype and suggests that inhibiting CD47 can both promote tumor phagocytosis and skew tumor macrophage subpopulations toward an anti-tumor phenotype. CC-90002 is currently being tested in two ongoing Phase I clinical studies in subjects with advanced solid and hematologic cancers (NCT02367196, NCT02641002)."

Acute Myelogenous Leukemia • Biosimilar • Breast Cancer • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. (PubMed, Ann Hematol) - P1 | "Despite no unexpected safety findings, the CC-90002-AML-001 study was discontinued in dose escalation for lack of monotherapy activity and evidence of ADAs. However, as other anti-CD47 agents in clinical trials are showing promising early results for AML and MDS, understanding preclinical and clinical differences between individual agents in this class will be of high importance."

Clinical • Journal • P1 data • Acute Myelogenous Leukemia • Cardiovascular • Cerebral Hemorrhage • Congestive Heart Failure • Febrile Neutropenia • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • Thrombocytopenia • SIRPA

Anti-CD47 Antibody, CC-90002, in Combination with Rituximab in Subjects with Relapsed and/or Refractory Non-Hodgkin Lymphoma (R/R NHL) (ASH 2019) - P1; "The CD47-SIRPα checkpoint inhibitor, CC-90002,plus rituximab demonstrated tolerability and modest clinical activity in this early-phase study of heavily pretreated R/R NHL subjects. AEs were predominantly grade 1/2; cytopenias were the most common AEs with dose-limiting thrombocytopenia observed at 30 mg/kg Q2W. In contrast to other CD47-targeting immunotherapies and consistent with results of preclinical studies of CC-90002, hemolysis at a starting dose of up to 30 mg/kg CC-90002 was not observed."

Clinical • Combination therapy • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results (ASH 2019) - P1; "CC-90002 showed a lack of objective responses in pts with R/R AML and high-risk MDS. The MTD and NTD were not established. The CC-90002-AML-001 study was discontinued in dose escalation for lack of preliminary monotherapy activity and evidence of ADAs in most pts."

Clinical • P1 data • Acute Myelogenous Leukemia • Cardiovascular • Cerebral Hemorrhage • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia

A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers (clinicaltrials.gov) - P1; N=60; Completed; Sponsor: Celgene; Active, not recruiting ➔ Completed

Trial completion • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • CD20

Modulation of CD47-SIRPα innate immune checkpoint axis with Fc-function detuned anti-CD47 therapeutic antibody. (PubMed, Cancer Immunol Immunother) - P1 | "Studies in a panel of hematological cancer cell lines showed concentration-dependent CC-90002-mediated phagocytosis in acute lymphoblastic leukemia, acute myeloid leukemia (AML), lenalidomide-resistant multiple myeloma (MM) cell lines and AML cells from patients...Furthermore, the role of macrophages in the CC-90002-mediated antitumor activity was demonstrated by transient depletion of macrophages with liposome-clodronate treatment. In non-human primates, CC-90002 displayed acceptable pharmacokinetic properties and a favorable toxicity profile. These data demonstrate the potential activity of CC-90002 across hematological malignancies and provided basis for clinical studies CC-90002-ST-001 (NCT02367196) and CC-90002-AML-001 (NCT02641002)."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Multiple Myeloma • Oncology • CD47

"Several trials CD47 molecules: Trillium (TTI-621), Alexo (ALX148), FortySeven Inc (Hu5F9-G4) & Celgene (CC-90002). Others not disclosed yet" (@jasonlukemd)

Biosimilar

A Study of CC-90002 in Subjects With Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS) (clinicaltrials.gov) - P1; N=28; Terminated; Sponsor: Celgene; N=71 ➔ 28; Trial completion date: Jul 2019 ➔ Jul 2018; Recruiting ➔ Terminated; Preliminary monotherapy data in relapsed/refractory AML and high-risk MDS did not offer a sufficiently encouraging profile for further dose escalation/expansion

Enrollment change • Trial completion date • Trial termination • Acute Myelogenous Leukemia • Biosimilar • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

CC-90002: Regulatory approval for NHL by 2022 (Celgene) - ASH 2018

Regulatory • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers (clinicaltrials.gov) - P1; N=60; Active, not recruiting; Sponsor: Celgene; Trial completion date: Feb 2020 ➔ Feb 2021; Trial primary completion date: Feb 2020 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date

A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers (clinicaltrials.gov) - P1; N=60; Active, not recruiting; Sponsor: Celgene; Recruiting ➔ Active, not recruiting; N=110 ➔ 60; Trial completion date: May 2021 ➔ Feb 2020; Trial primary completion date: May 2021 ➔ Feb 2020

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

Blocking "don't eat me" signal of CD47-SIRPα in hematological malignancies, an in-depth review. (PubMed, Blood Rev) - "Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma."

Journal • Review

A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers (clinicaltrials.gov) - P1; N=110; Recruiting; Sponsor: Celgene; N=65 ➔ 110

Clinical • Enrollment change

RRx-001 is a Phase 3-Ready small molecule dual inhibitor of CD47 and SIRPalpha (SITC 2018) - "One area of intense interest is the targeting of CD47 with monoclonal antibodies (mAbs), three of which, Hu5F9-G4, CC-90002, and TTI-621, have proceeded to clinical trials [1]. Dual downregulation of CD47 and SIRPα by RRx-001 results in TAM repolarization and phagocytosis of tumor cells. Depletion of macrophages by clodronate in tumorbearing mice reduced the antitumor effects of RRx- 001 and further suggests that the target of RRx-001 is the macrophage."

IO Biomarker • P3 data