Lancet Oncol: CD40 astrogenic monoclonal antibody APX005M combined chemotherapy to treat metastatic pancreatic cancer

For metastatic pancreatic cancer, standard chemotherapy still performs poorly.
tumors induced by the combined chemotherapy department of excited CD40 monoclonal antibodies induced T-cell-dependent tumors in mice to subside and improve survival.
the study was designed to assess the safety of APX005M (sotigalimab) and Gissytabin combined nab-yew alcohol and or non-navutamol to treat patients with pancreatic cancer to determine the recommended phase 2 dose.
the study was a non-randomized, open-label, multi-center, multi-group Phase 1b trial that recruited untreated metastatic pancreatic cancer patients over the age of 18.
all patients were treated with gisithambin (1000 mg/m2, static drops) and nab-yew alcohol (125 mg/m2, static drops).
patients in the B1 and C1 groups received APX005M (static drop) treatment of 0.1 mg/kg and APX005M (static drop) of 0.3 mg/kg in groups B2 and C2.
in the C1 and C2 groups were also treated with navuda (240 mg).
adverse reaction rates and dose-limiting toxicity (DLT) were found at the main endpoints, and the recommended phase 2 dose of APX005M was determined.
the objective mitigation rate is the secondary end point.
August 22, 2017 - July 10, 2018, 42 patients were screened, 30 of whom were included in the study and received at least one dose of the drug; medium follow-up for 17.8 months (B1 group 22.0 months, B2 group 18.2 months, C1 group 17.9 months, C2 group 15.9 months).
two cases of DLT, both febrative neutral granulocyte reduction, were observed in one patient in group B2 (level 3) and one patient in group C1 (level 4).
the most common level 3-4 treatment-related adverse reaction events were a decrease in lymphocyte count (20 cases ( 67%), B1 group, B2 group, C1 group, C2 group 5 cases, 7 cases, 4 cases, 4 cases), Anemia (11 s 37%; 2 cases, 4 cases, 1 case, 2 cases) and neutral granulocyte reduction (9 cases (30%); 3 cases, 3 cases, 1 case, 2 cases).
14 (47%) of the 30 patients in the patients, one case each in the B1 group, B2 group and C1 group, and 2 cases in the C2 group, had serious adverse reactions associated with treatment.
the most common severe adverse reactions were fever (6 cases (20 per cent), 1 case in group B2, 3 cases in group C1, and 2 cases in group C2.
two chemotherapy-related deaths (death from adverse reactions: 1 case of sepsis in group B1 and 1 case of sepsis shock in group C1).
phase 2 dose for APX005M is 0.3 mg/kg.
14 (58%) of the 24 DLT assessable patients received remission (B1, C1, C2 and 2 in Group B).
APX005M and Gixitabin combined nab-yew alcohol and or no navutamol to treat pancreatic cancer patients with good tolerance, and showed some clinical activity.
if proven in a later clinical trial, the treatment option may be used in this group of patients as an alternative to a single standard chemotherapy treatment.
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