Combination Therapy for Cancer
This disclosure provides combination therapies comprising an anti-BCMA antigen binding protein, such as belantamab mafodotin; an immunomodulatory imide drug (IMiD); a proteasome inhibitor; and a corticosteroid. This disclosure also provides combination therapies for treating newly diagnosed multiple myeloma.
1 . A combination therapy, comprising:
(a) a therapeutically effective dose of an anti-BCMA antigen binding protein;
(b) a therapeutically effective dose of a proteasome inhibitor;
(c) a therapeutically effective dose of an immunomodulatory imide drug; and
(d) a therapeutically effective amount of a corticosteroid,
wherein the anti-BCMA antigen binding protein is belantamab mafodotin, the proteasome inhibitor is bortezomib, the immunomodulatory imide drug is lenalidomide and the corticosteroid is dexamethasone.
2 .- 6 . (canceled)
7 . The combination therapy of claim 61 , which comprises:
(a) administration of belantamab mafodotin according to a schedule selected from the group consisting of
(i) 1.9 mg/kg dose of belantamab mafodotin Q3/4W, 1.9 mg/kg on Day 1 of every cycle;
(ii) a 1.4 mg/kg dose of belantamab mafodotin Q6/8W, 1.4 mg/kg on Day 1 of every other cycle;
(iii) a 1.9 mg/kg dose of belantamab mafodotin Q6/8W on Day 1 of every other cycle;
(iv) a 1.0 mg/kg dose of belantamab mafodotin Q3/4W, 1.0 mg/kg on Day 1 of every cycle;
(v) a 1.4 mg/kg dose of belantamab mafodotin Q3/4W, 1.4 mg/kg on Day 1 of every cycle;
(vi) a 1.4 mg/kg dose of belantamab mafodotin on Day 1 of cycle 1 and 1.0 mg/kg on Day 1 of every third cycle from cycle 4;
(vii) a 1.9 mg/kg dose of belantamab mafodotin on Day 1 of cycle 1 and 1.4 mg/kg of belantamab mafodotin on Day 1 of every third cycle from cycle 4;
(viii) a 1.9 mg/kg dose of belantamab mafodotin on Day 1 of cycle 1 and cycle 4 and a 1.4 mg/kg of belantamab mafodotin on Day 1 of every third cycle from cycle 7;
(ix) a 1.4 mg/kg dose of belantamab mafodotin on Day 1 of cycle 1 and cycle 3 and a 1.0 mg/kg dose of belantamab mafodotin on Day 1 of every third cycle from cycle 6; and
(x) a 1.0 mg/kg dose of belantamab mafodotin on Day 1 of cycle 1 and cycle 5 and a 1.0 mg/kg dose of belantamab mafodotin on day 1 of every third cycle from cycle 9;
(b) administration of bortezomib at a dose of 1.3 mg/m 2 subcutaneously (SC) on Days 1, 4, 8, and 11 of every 21-day cycle for eight induction Cycles;
(c) administration of lenalidomide (1) at a dose of 25 mg, orally, on Days 1-14 of a 21-day cycle for eight induction Cycles or (2) at 10 mg daily on Days 1-14 of each 21-day cycle if the individual has eGFR 30-60 mL/min/1.73 m 2 ; and
(d) administration of dexamethasone orally at a dose of 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of a 21-day cycle for eight induction Cycles.
8 . The combination therapy of claim 7 , further comprising a second combination therapy, comprising:
(a) a therapeutically effective dose of an anti-BCMA antigen binding protein;
(b) a therapeutically effective dose of an immunomodulatory imide drug; and
(c) a therapeutically effective amount of a corticosteroid,
wherein the anti-BCMA antigen binding protein is belantamab mafodotin, the immunomodulatory imide drug is lenalidomide, and the corticosteroid is dexamethasone.
9 .- 12 . (canceled)
13 . The combination therapy of claim 12 , wherein administration of the second combination therapy comprises:
(a) intravenous administration of belantamab mafodotin on a schedule selected from the group consisting of
(i) administration on Day 1 of every 28-day cycle;
(ii) administration on Day 1 of every other 28-day cycle; and
(iii) administration on Day 1 of every third 28-day cycle;
(b) oral administration of lenalidomide at a dose of (i) 25 mg on Days 1-21 of each 28-day cycle or (ii) 10 mg on Days 1-21 of each 28-day cycle; and
(c) oral administration of dexamethasone at a dose of 20 mg or 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.
14 . A method of treating newly diagnosed multiple myeloma, comprising administering to an individual in need thereof a combination therapy of claim 1 .
15 . The method of claim 14 , wherein the individual is ineligible for autologous stem cell transplant.
16 . The method of claim 14 , further comprising a maintenance therapy comprising a second combination therapy, comprising:
(a) a therapeutically effective dose of an anti-BCMA antigen binding protein;
(b) a therapeutically effective dose of an immunomodulatory imide drug; and
(c) a therapeutically effective amount of a corticosteroid,
wherein the anti-BCMA antigen binding protein is belantamab mafodotin, the immunomodulatory imide drug is lenalidomide, and the corticosteroid is dexamethasone.
17 .- 20 . (canceled)
21 . A method of treating multiple myeloma in a subject, comprising administering to the subject:
(a) a therapeutically effective dose of an anti-BCMA antigen binding protein;
(b) a therapeutically effective dose of a proteasome inhibitor;
(c) a therapeutically effective dose of an immunomodulatory imide drug; and
(d) a therapeutically effective amount of a corticosteroid,
wherein the anti-BCMA antigen binding protein is belantamab mafodotin, and wherein the belantamab mafodotin is administered intravenously to the subject according to a schedule selected from the group consisting of:
(i) a 1.9 mg/kg dose of belantamab mafodotin on day 1 of every cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(ii) a 1.4 mg/kg dose of belantamab mafodotin on day 1 of every other cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(iii) a 1.9 mg/kg dose of belantamab mafodotin on day 1 of every other cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(iv) a 1.0 mg/kg dose of belantamab mafodotin on day 1 of every cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(v) a 1.4 mg/kg dose of belantamab mafodotin on day 1 of every cycle for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(vi) a 1.4 mg/kg dose of belantamab mafodotin on day 1 of cycle 1 and a 1.0 mg/kg dose of belantamab mafodotin on day 1 of every third cycle from cycle 4 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(vii) a 1.9 mg/kg dose of belantamab mafodotin on day 1 of cycle 1 and a 1.4 mg/kg dose of belantamab mafodotin on day 1 of every third cycle from cycle 4 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(viii) a 1.9 mg/kg dose of belantamab mafodotin on day 1 of cycle 1 and cycle 4 and a 1.4 mg/kg dose of belantamab mafodotin on day 1 of every third cycle from cycle 7 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
(ix) a 1.4 mg/kg dose of belantamab mafodotin on day 1 of cycle 1 and cycle 3 and a 1.0 mg/kg dose of belantamab mafodotin on day 1 of every third cycle from cycle 6 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days; and
(x) a 1.0 mg/kg dose of belantamab mafodotin on day 1 of cycle 1 and cycle 5 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
wherein the proteasome inhibitor is bortezomib, and wherein the bortezomib is administered to the subject at a dose of 1.3 mg/m 2 subcutaneously (SC) on days 1, 4, 8, and 11 of every 21-day cycle for eight induction treatment cycles;
wherein the immunomodulatory imide drug is lenalidomide, and wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
wherein the corticosteroid is dexamethasone, and wherein the dexamethasone is administered to the subject orally at a dose of (i) 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years or has a body mass index (BMI) of <18.5.
22 . The method of claim 21 , further comprising administering to the subject, after the eight induction treatment cycles, a maintenance therapy comprising:
(a) a therapeutically effective dose of an anti-BCMA antigen binding protein;
(b) a therapeutically effective dose of an immunomodulatory imide drug; and
(c) a therapeutically effective amount of a corticosteroid,
wherein the anti-BCMA antigen binding protein is belantamab mafodotin, and wherein the belantamab mafodotin is administered intravenously according to a schedule selected from the group consisting of
(i) administration on day 1 of every 28-day cycle;
(ii) administration on day 1 of every other 28-day cycle; and
(iii) administration on day 1 of every third 28-day cycle;
wherein the immunomodulatory imide drug is lenalidomide, and wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-21 of each 28-day cycle or (ii) 10 mg on days 1-21 of each 28-day cycle if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
wherein the corticosteroid is dexamethasone, and wherein the dexamethasone is administered orally to the subject at a dose of (i) 40 mg on days 1, 8, 15 and 22 of each 28-day cycle or (ii) 20 mg on days 1, 8, 15, and 22 of each 28-day cycle if the subject is older than 75 years or has a body mass index (BMI) of <18.5.
23 .- 27 . (canceled)
28 . The method of claim 21 , comprising administering to the subject:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg/kg on day 1 of cycle 1 and at a dose of 1.0 mg/kg on day 1 of every third cycle from cycle 4 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
bortezomib, wherein the bortezomib is administered to the subject at a dose of 1.3 mg/m 2 subcutaneously (SC) on days 1, 4, 8, and 11 of every 21-day cycle for eight induction treatment cycles;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered to the subject orally at a dose of (i) 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years or has a body mass index (BMI) of <18.5; and
administering to the subject, after the eight induction treatment cycles, a maintenance therapy comprising:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg/kg on day 1 of every third cycle from cycle 9 onwards, wherein each cycle is 28 days;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-21 of each 28-day cycle or (ii) 10 mg on days 1-21 of each 28-day cycle if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered orally to the subject at a dose of (i) 40 mg on days 1, 8, 15 and 22 of each 28-day cycle or (ii) 20 mg on days 1, 8, 15, and 22 of each 28-day cycle if the subject is older than 75 years or has a body mass index (BMI) of <18.5.
29 . The method of claim 21 , comprising administering to the subject:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg/kg on day 1 of cycle 1 and at a dose of 1.4 mg/kg dose on day 1 of every third cycle from cycle 4 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
bortezomib, wherein the bortezomib is administered to the subject at a dose of 1.3 mg/m 2 subcutaneously (SC) on days 1, 4, 8, and 11 of every 21-day cycle for eight induction treatment cycles;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered to the subject orally at a dose of (i) 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years or has a body mass index (BMI) of <18.5; and
administering to the subject, after the eight induction treatment cycles, a maintenance therapy comprising:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg/kg on day 1 of every third cycle from cycle 9 onwards, wherein each cycle is 28 days;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-21 of each 28-day cycle or (ii) 10 mg on days 1-21 of each 28-day cycle if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered orally to the subject at a dose of (i) 40 mg on days 1, 8, 15 and 22 of each 28-day cycle or (ii) 20 mg on days 1, 8, 15, and 22 of each 28-day cycle if the subject is older than 75 years or has a body mass index (BMI) of <18.5.
30 . The method of claim 21 , comprising administering to the subject:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.9 mg/kg on day 1 of cycle 1 and cycle 4 and at a dose of 1.4 mg/kg dose on day 1 of every third cycle from cycle 7 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
bortezomib, wherein the bortezomib is administered to the subject at a dose of 1.3 mg/m 2 subcutaneously (SC) on days 1, 4, 8, and 11 of every 21-day cycle for eight induction treatment cycles;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered to the subject orally at a dose of (i) 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years or has a body mass index (BMI) of <18.5; and
administering to the subject, after the eight induction treatment cycles, a maintenance therapy comprising:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg/kg on day 1 of every third cycle from cycle 9 onwards, wherein each cycle is 28 days;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-21 of each 28-day cycle or (ii) 10 mg on days 1-21 of each 28-day cycle if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered orally to the subject at a dose of (i) 40 mg on days 1, 8, 15 and 22 of each 28-day cycle or (ii) 20 mg on days 1, 8, 15, and 22 of each 28-day cycle if the subject is older than 75 years or has a body mass index (BMI) of <18.5.
31 . The method of claim 21 , comprising administering to the subject:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.4 mg/kg on day 1 of cycle 1 and cycle 3 and at a dose of 1.0 mg/kg dose on day 1 of every third cycle from cycle 6 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
bortezomib, wherein the bortezomib is administered to the subject at a dose of 1.3 mg/m 2 subcutaneously (SC) on days 1, 4, 8, and 11 of every 21-day cycle for eight induction treatment cycles;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered to the subject orally at a dose of (i) 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years or has a body mass index (BMI) of <18.5; and
administering to the subject, after the eight induction treatment cycles, a maintenance therapy comprising:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg/kg on day 1 of every third cycle from cycle 9 onwards, wherein each cycle is 28 days;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-21 of each 28-day cycle or (ii) 10 mg on days 1-21 of each 28-day cycle if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered orally to the subject at a dose of (i) 40 mg on days 1, 8, 15 and 22 of each 28-day cycle or (ii) 20 mg on days 1, 8, 15, and 22 of each 28-day cycle if the subject is older than 75 years or has a body mass index (BMI) of <18.5.
32 . The method of claim 21 , comprising administering to the subject:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg/kg on day 1 of cycle 1 and cycle 5 for eight induction treatment cycles, wherein each induction treatment cycle is 21 days;
bortezomib, wherein the bortezomib is administered to the subject at a dose of 1.3 mg/m 2 subcutaneously (SC) on days 1, 4, 8, and 11 of every 21-day cycle for eight induction treatment cycles;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on each of days 1-14 of each 21-day cycle for eight induction treatment cycles if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered to the subject orally at a dose of (i) 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles or (ii) 10 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for eight induction treatment cycles if the subject is older than 75 years or has a body mass index (BMI) of <18.5; and
administering to the subject, after the eight induction treatment cycles, a maintenance therapy comprising:
belantamab mafodotin, wherein the belantamab mafodotin is administered intravenously to the subject at a dose of 1.0 mg/kg on day 1 of every third cycle from cycle 9 onwards, wherein each cycle is 28 days;
lenalidomide, wherein the lenalidomide is administered orally to the subject at a dose of (i) 25 mg on each of days 1-21 of each 28-day cycle or (ii) 10 mg on days 1-21 of each 28-day cycle if the subject has eGFR 30-60 mL/min/1.73 m 2 ; and
dexamethasone, wherein the dexamethasone is administered orally to the subject at a dose of (i) 40 mg on days 1, 8, 15 and 22 of each 28-day cycle or (ii) 20 mg on days 1, 8, 15, and 22 of each 28-day cycle if the subject is older than 75 years or has a body mass index (BMI) of <18.5.
33 . The method of claim 21 , wherein the multiple myeloma is newly diagnosed multiple myeloma.
34 . The method of claim 33 , wherein the subject is ineligible for autologous stem cell transplant.