Bispecific antibody against CD3 and CD20 in combination therapy for treating follicular lymphoma
AssigneeGenmab A/S
InventorsBrian Elliott, Tahamtan Ahmadi, Christopher W. L. Chiu, Esther C. W. Breij
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Abstract
Provided are methods of clinical treatment of follicular lymphoma (for example, relapsed and/or refractory follicular lymphoma) in human subjects using a bispecific antibody which binds to CD3 and CD20 in combination with standard of care regimens of rituximab and bendamustine.
Claims27
A method of treating follicular lymphoma in a human subject, the method comprising administering to the subject a bispecific antibody and an effective amount of rituximab and bendamustine, wherein the bispecific antibody comprises:
- (i) a first binding arm comprising a first antigen-binding region which binds to human CD3c (epsilon) and comprises a variable heavy chain (VH) region and a variable light chain (VL) region, wherein the VH region comprises the CDR1, CDR2 and CDR3 sequences that are in the VH region sequence of SEQ ID NO:
- 6, and the VL region comprises the CDR1, CDR2 and CDR3 sequences that are in the VL region sequence of SEQ ID NO:
- 7;
- and
- (ii) a second binding arm comprising a second antigen-binding region which binds to human CD20 and comprises a VH region and a VL region, wherein the VH region comprises the CDR1, CDR2 and CDR3 sequences that are in the VH region sequence of SEQ ID NO:
- 13, and the VL region comprises the CDR1, CDR2 and CDR3 sequences that are in the VL region sequence of SEQ ID NO:
- 14;
- wherein the bispecific antibody is administered at a dose of 24 mg or 48 mg, and wherein rituximab, bendamustine, and the bispecific antibody are administered in 28-day cycles,
- wherein the bispecific antibody, rituximab, and bendamustine are administered in the same cycle for the first 6 cycles, and the bispecific antibody is administered alone for subsequent cycles, and wherein a priming dose of the bispecific antibody is administered on day 1 of cycle 1 and an intermediate dose is administered on day 8 of cycle 1 before the dose of 24 mg or 48 mg on days 15 and 22 of cycle 1.
A method of treating follicular lymphoma in a human subject, the method comprising administering to the subject a bispecific antibody and an effective amount of rituximab and bendamustine, wherein the bispecific antibody comprises a first heavy chain and a first light chain comprising the amino acid sequences set forth in SEQ ID NOs:
- 24 and 25, respectively, and a second heavy chain and a second light chain comprising the amino acid sequences set forth in SEQ ID NOs:
- 26 and 27, respectively;
- wherein the bispecific antibody is administered at a dose of 24 mg, and wherein rituximab, bendamustine, and the bispecific antibody are administered in 28-day cycles, and wherein:
- (a) the bispecific antibody is administered as follows:
- (i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 24 mg is administered on days 15 and 22;
- (ii) in cycles 2 and 3, a dose of 24 mg is administered on days 1, 8, 15, and 22;
- (iii) in cycles 4-9, a dose of 24 mg is administered on days 1 and 15;
- and
- (iv) in cycle 10 and subsequent cycles, a dose of 24 mg is administered on day 1;
- (b) rituximab is administered on day 1 in cycles 1-6;
- and
- (c) bendamustine is administered on days 1 and 2 in cycles 1-6.
A method of treating follicular lymphoma in a human subject, the method comprising administering to the subject a bispecific antibody and an effective amount of rituximab and bendamustine, wherein the bispecific antibody comprises a first heavy chain and a first light chain comprising the amino acid sequences set forth in SEQ ID NOs:
- 24 and 25, respectively, and a second heavy chain and a second light chain comprising the amino acid sequences set forth in SEQ ID NOs:
- 26 and 27, respectively;
- wherein the bispecific antibody is administered at a dose of 48 mg, and wherein rituximab, bendamustine, and the bispecific antibody are administered in 28-day cycles, and wherein:
- (a) the bispecific antibody is administered as follows:
- (i) in cycle 1, a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a dose of 48 mg is administered on days 15 and 22;
- (ii) in cycles 2 and 3, a dose of 48 mg is administered on days 1, 8, 15, and 22;
- (iii) in cycles 4-9, a dose of 48 mg is administered on days 1 and 15;
- and
- (iv) in cycle 10 and subsequent cycles, a dose of 48 mg is administered on day 1;
- (b) rituximab is administered on day 1 in cycles 1-6;
- and
- (c) bendamustine is administered on days 1 and 2 in cycles 1-6.
Dependencies are inferred from the claim text.