TY - JOUR
T1 - A Pilot Study of the PD-1 Targeting Agent AMP-224 Used With Low-Dose Cyclophosphamide and Stereotactic Body Radiation Therapy in Patients With Metastatic Colorectal Cancer
AU - Floudas, Charalampos S.
AU - Brar, Gagandeep
AU - Mabry-Hrones, Donna
AU - Duffy, Austin G.
AU - Wood, Bradford
AU - Levy, Elliot
AU - Krishnasamy, Venkatesh
AU - Fioravanti, Suzanne
AU - Bonilla, Cecilia M.
AU - Walker, Melissa
AU - Morelli, Maria Pia
AU - Kleiner, David E.
AU - Steinberg, Seth M.
AU - Figg, William D.
AU - Greten, Tim F.
AU - Xie, Changqing
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/12
Y1 - 2019/12
N2 - Background: The prognosis of metastatic colorectal cancer (mCRC) is poor. We assessed the feasibility, safety, and efficacy of the anti-programmed cell death 1 fusion protein AMP-224 in combination with low-dose cyclophosphamide and stereotactic body radiation (SBRT) treatment in patients with mCRC refractory to standard chemotherapy. Patients and Methods: Fifteen patients were enrolled. Six received SBRT 8 Gy on day 0 (dose level 1), whereas 9 received 8 Gy on days −2 to day 0. All received cyclophosphamide 200 mg/m2 intravenously (I.V.) on day 0. On day 1, both groups received AMP-224 10 mg/kg I.V., repeated every 2 weeks for a total of 6 doses. Primary end points were feasibility and safety. Results: Ten (67%) patients completed 6 doses of AMP-224; 5 patients (33%) discontinued treatment because of disease progression. No dose-limiting toxicity was observed; 9 patients (60%) experienced treatment-related adverse events, all Grade 1 or 2. No objective response was noted; 3 patients (20%) had stable disease. Median progression-free survival and overall survival were 2.8 months (95% confidence interval [CI], 1.2-2.8 months) and 6.0 months (95% CI, 2.8-9.6 months), respectively. M2 macrophage polarization was present in the pretreatment tumor biopsy samples, but not post-treatment samples. Conclusion: AMP-224 in combination with SBRT and low-dose cyclophosphamide was well tolerated, however, no significant clinical benefit was observed in patients with mCRC.
AB - Background: The prognosis of metastatic colorectal cancer (mCRC) is poor. We assessed the feasibility, safety, and efficacy of the anti-programmed cell death 1 fusion protein AMP-224 in combination with low-dose cyclophosphamide and stereotactic body radiation (SBRT) treatment in patients with mCRC refractory to standard chemotherapy. Patients and Methods: Fifteen patients were enrolled. Six received SBRT 8 Gy on day 0 (dose level 1), whereas 9 received 8 Gy on days −2 to day 0. All received cyclophosphamide 200 mg/m2 intravenously (I.V.) on day 0. On day 1, both groups received AMP-224 10 mg/kg I.V., repeated every 2 weeks for a total of 6 doses. Primary end points were feasibility and safety. Results: Ten (67%) patients completed 6 doses of AMP-224; 5 patients (33%) discontinued treatment because of disease progression. No dose-limiting toxicity was observed; 9 patients (60%) experienced treatment-related adverse events, all Grade 1 or 2. No objective response was noted; 3 patients (20%) had stable disease. Median progression-free survival and overall survival were 2.8 months (95% confidence interval [CI], 1.2-2.8 months) and 6.0 months (95% CI, 2.8-9.6 months), respectively. M2 macrophage polarization was present in the pretreatment tumor biopsy samples, but not post-treatment samples. Conclusion: AMP-224 in combination with SBRT and low-dose cyclophosphamide was well tolerated, however, no significant clinical benefit was observed in patients with mCRC.
KW - Immunotherapy
KW - Macrophages
KW - PD-L2 Ligand
KW - Programmed Cell Death 1 Protein
KW - Stereotactic Radiation Therapy
UR - http://www.scopus.com/inward/record.url?scp=85069654179&partnerID=8YFLogxK
U2 - 10.1016/j.clcc.2019.06.004
DO - 10.1016/j.clcc.2019.06.004
M3 - Article
C2 - 31351862
AN - SCOPUS:85069654179
SN - 1533-0028
VL - 18
SP - e349-e360
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 4
ER -