A phase Ib study of the anti-CD47 antibody magrolimab with the PD-L1 inhibitor avelumab (A) in solid tumor (ST) and ovarian cancer (OC) patients.

Authors

null

Nehal J. Lakhani

START-Midwest, Grand Rapids, MI

Nehal J. Lakhani, Amita Patnaik, John B. Liao, John William Moroney, David S. Miller, Gini F. Fleming, Matt Axt, Yan V. Wang, Balaji Agoram, Jens-Peter Volkmer, Roy Maute, Andreas Schroeder, Isagani Chico, Mark Chao, Chris H.M. Takimoto, Kathleen N. Moore

Organizations

START-Midwest, Grand Rapids, MI, South Texas Accelerated Research Therapeutics, San Antonio, TX, University of Washington, Seattle, WA, University of Chicago Medicine, Chicago, IL, The University of Texas Southwestern Medical Center, Dallas, TX, The University of Chicago Medicine, Chicago, IL, Forty Seven, Inc, Menlo Park, CA, Forty Seven, Inc., Menlo Park, CA, Forty Seven, Menlo Park, CA, Forty Seven Inc., Menlo Park, CA, Merck KGaA, Darmstadt, Germany, Forty Seven Inc, San Francisco, CA, Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK

Research Funding

Pharmaceutical/Biotech Company
Forty Seven, Inc and Merck KGaA.

Background: Magrolimab (M, Hu5F9-G4) is an antibody targeting CD47, a “don’t eat me” signal for macrophages that enhances ovarian cancer cell phagocytosis in preclinical models in combination with the PD-L1 inhibitor avelumab. CD47 blockade can also enhance cross-priming of T cells. Methods: In Part 1 (P1) M+A doses were escalated in ST patients (pts) while Part 2 (P2) enrolled platinum-resistant or refractory OC pts. All received a 1 mg/kg Day 1 priming dose of M to mitigate on-target anemia due to macrophage-mediated extravascular hemolysis followed by 30 or 45 mg/kg maintenance doses in P1 or 45 mg/kg in P2, in combination with 800 mg of A Q2 wks. Results: In the 34 total pts (13 in P1 and 21 in P2), median age was 66 years (range 47-88), and median # of prior therapies was 5 (range 1-10). In P1, no dose limiting toxicities occurred. In P1+P2, no Grade (G) 4 or 5 treatment-related adverse events (TRAEs) occurred. TRAEs of any G in > 20% pts included headache 62%, fatigue 47%, infusion related reaction 44%, pyrexia 38%, chills 35%, nausea 35%, anemia 24%, and vomiting 21%. In P1, a patient (pt) with metastatic papillary adenocarcinoma of the finger on 45 mg/kg of M had a confirmed partial response (PR) lasting for 4 months before progressing. In P2, 1 pt had an unconfirmed PR but progressed per RECIST v1.1 on the next scan achieving a best response of stable disease (SD). In the 18 OC P1+P2 pts with at least one response evaluation, 56% had SD and 44% had progression. Analysis of tumor biopsies for immune cells infiltration and CD47, PD-L1, and other marker expression is ongoing. In the 13 OC tumors analyzed to date, only 2 were PD-L1 positive. One PD-L1+ tumor had PD-L1 expression only on infiltrating immune cells. The other PD-L1+ had tumor cell expression and was the only OC pt with tumor shrinkage. This supports the potential importance of PD-L1 expression for this combination. Pharmacokinetic profiles will be presented. Conclusions: M+A is a novel, well-tolerated combination treatment regimen with 1 observed PR in a ST pt and a 56% SD rate in OC pts. Tumor shrinkage was noted in the only OC pt with tumor cell expression of PD-L1 which warrants further evaluation in PD-L1+ OC pts. Clinical trial information: NCT03558139

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Abstract Details

Meeting

2020 ASCO-SITC Clinical Immuno-Oncology Symposium

Session Type

Poster Session

Session Title

Poster Session A

Track

Breast and Gynecologic Cancers,Developmental Therapeutics,Genitourinary Cancer,Head and Neck Cancer,Lung Cancer,Melanoma/Skin Cancers,Gastrointestinal Cancer,Combination Studies,Implications for Patients and Society,Miscellaneous Cancers,Hematologic Malignancies

Sub Track

Immune Checkpoints and Stimulatory Receptors

Clinical Trial Registration Number

NCT03558139

Citation

J Clin Oncol 38, 2020 (suppl 5; abstr 18)

Abstract #

18

Poster Bd #

B12

Abstract Disclosures

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