Dosage and administration of anti-EGFR therapeutics
Methods for optimizing a therapeutic response in a patient (e.g., a cancer patient) to an anti-EGFR therapy, and methods for preventing or ameliorating infusion reactions in a patient receiving an anti-EGFR therapy are disclosed.
1. A method of administering a mixture of three monoclonal IgG1 anti-EGFR antibodies to a human cancer patient,
the method comprising initially administering the mixture to the patient as a first and a second intravenous infusion over a two week cycle as priming doses in sequence as set forth in the following table:
Infusion
Infusion
Mixture
Cumulative
Rate
Rate
Infused
Mixture
Infusion
Sequence 1
(mg/hr)
(mg)
Infused (mg)
1 st Infusion
1 st Rate
25
12.5
12.5
(Priming Week 1)
2 nd Rate
50
25.0
37.5
3 rd Rate
100
187.5
225.0
2 nd Infusion
1 st Rate
25
12.5
12.5
(Priming Week 2)
2 nd Rate
50
25.0
37.5
3 rd Rate
100
50.0
87.5
4 th Rate
200
362.5
450
1 per infusion
wherein the 1 st infusion of the mixture is administered during the priming week 1 at the 1 st rate for a 1/2 hour, immediately followed by the 2 nd rate for a second 1/2 hour, immediately followed by the 3 rd rate until all of the first dose and 225 mg of mixture has been administered;
wherein the 2 nd infusion of the mixture is administered during priming week 2 at the 1 st rate for a 1/2 hour, immediately followed by the 2 nd rate for the second 1/2 hour, immediately followed by the 3 rd rate for a 1/2 hour, immediately followed by the 4 th rate until all of the first dose and 450 mg of mixture has been administered;
wherein, prior to each infusion of the mixture of anti-EGFR antibodies, diphenhydramine is administered to the patient orally or intravenously at a dose of 25 mg-50 mg and methylprednisolone is administered to the patient intravenously at a dose of 25-125 mg; and
wherein the mixture comprises:
i) a first monoclonal antibody comprising heavy chain CDRs 1, 2 and 3 set forth in SEQ ID NOs: 7, 8 and 9 respectively, and light chain CDRs 1, 2 and 3 set forth in SEQ ID NOs: 10, 11 and 12 respectively;
ii) a second monoclonal antibody comprising heavy chain CDRs 1, 2 and 3 set forth in SEQ ID NOs: 13, 14 and 15 respectively and light chain CDRs 1, 2 and 3 set forth in SEQ ID NOs: 16, 17, and 18 respectively; and
iii) a third monoclonal antibody comprising heavy chain CDRs 1, 2 and 3 set forth in SEQ ID NOs: 19, 20 and 21 respectively, and light chain CDRs 1, 2 and 3 set forth in SEQ ID NOs: 22, 23 and 24 respectively;
wherein the first antibody, the second antibody, and the third antibody are formulated in a mixture at a molar ratio to each other of 2:2:1, respectively;
wherein the mixture of three monoclonal IgG1 anti-EGFR antibodies is administered to a human cancer patient diagnosed with colorectal cancer, in combination with liposomal irinotecan.
2. The method of claim 1 , wherein the dose of methylprednisolone is 125 mg.
3. The method of claim 1 , wherein the first antibody comprises a heavy chain variable region comprising SEQ ID NO:1 and a light chain variable region comprising SEQ ID NO:2, the second antibody comprises a heavy chain variable region comprising SEQ ID NO:3 and a light chain variable region comprising SEQ ID NO:4; and the third antibody comprises a heavy chain variable region comprising SEQ ID NO:5 and a light chain variable region comprising SEQ ID NO:6.
4. The method of claim 1 , wherein, prior to each infusion of the mixture of anti-EGFR antibodies, acetaminophen is administered to the patient at a dose of 650 mg.
5. The method of claim 1 , wherein the mixture of three monoclonal IgG1 anti-EGFR antibodies is MM-151.
6. The method of claim 1 , wherein the mixture of three monoclonal IgG1 anti-EGFR antibodies is administered in further combination with 5-fluorouracil and leucovorin.