Uses of immunoconjugates targeting CD138

A method for treating a disease associated with target cells expressing CD138 comprising:

• administering to a subject in need thereof an immunoconjugate comprising at least one engineered targeting antibody targeting CD138 expressing cells, and
• at least one maytansinoid, wherein said engineered targeting antibody is functionally attached to said maytansinoid to form said immunoconjugate, wherein at least a part of the engineered targeting antibody confers IgG4 isotype properties, wherein the immunoconjugate is administered in intervals of less than 11.1 days within a period of 21 days constituting a multiple dose regimen, wherein the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD and wherein said AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle, wherein said administration is followed, after at least two 21 day treatment cycles, each followed by a resting period, by a further administration of the immunoconjugate or a pharmaceutical composition comprising the immunoconjugate.

A method for treating a disease associated with target cells expressing CD138 comprising:

• administering to a subject in need thereof an immunoconjugate comprising at least one engineered targeting antibody targeting CD138 expressing cells, and
• at least one maytansinoid, wherein said engineered targeting antibody is functionally attached to said maytansinoid to form said immunoconjugate, wherein at least a part of the engineered targeting antibody confers IgG4 isotype properties, wherein the immunoconjugate is administered in intervals of less than 11.1 days within a period of 21 days constituting a multiple dose regimen, wherein the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD and wherein said AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle, further comprising determining 0-4 hours, including at about 1, 2, or 3, following a completion of administering said immunoconjugate or a pharmaceutical composition comprising the same, a reference level (RL) of an said immunoconjugate or of an efficacy blood parameter in a body fluid of a patient,
• determining in a subsequent administration of said immunoconjugate, at 0-4 hours following a completion of said subsequent administration, a subsequent level (SL) of an said immunoconjugate or efficacy blood parameter,
• comparing the RL to the SL,
• (i) determining RL>SL, and increasing the aggregate dose in a treatment cycle following said subsequent administration by 5-100%, including 10-50% or 20-30%, and/or
• (ii) determining RL<SL, and decreasing the aggregate dose in a treatment cycle following said subsequent administration by 5-100%, including 10-50% or 20-30%.

A method for treating a disease associated with target cells expressing CD138 comprising:

• administering to a subject in need thereof an immunoconjugate comprising at least one engineered targeting antibody targeting CD138 expressing cells, and at least one maytansinoid, wherein said engineered targeting antibody is functionally attached to said maytansinoid to form said immunoconjugate, wherein at least a part of the engineered targeting antibody confers IgG4 isotype properties, wherein the immunoconjugate is administered in intervals of less than 11.1 days within a period of 21 days constituting a multiple dose regimen, wherein the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD and wherein said AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle, wherein said subject suffers from a solid tumor comprising target cells which express CD138 and wherein said solid tumor is refractory to cancer hormone therapy or chemotherapy or the subject has relapsed after hormone therapy or chemotherapy, wherein said administration results in at least tumor growth delay or tumor stasis.

A method for treating a disease associated with target cells expressing CD138 comprising:

• administering to a subject in need thereof an immunoconjugate comprising at least one engineered targeting antibody targeting CD138 expressing cells, and at least one maytansinoid, wherein said engineered targeting antibody is functionally attached to said maytansinoid to form said immunoconjugate, wherein at least a part of the engineered targeting antibody confers IgG4 isotype properties, wherein the immunoconjugate is administered in intervals of less than 11.1 days within a period of 21 days constituting a multiple dose regimen, wherein the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD and wherein said AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle, wherein the administration of said immunoconjugate or pharmaceutical composition comprising the immunoconjugate is preceded by an administration of unconjugated antibody targeting CD138 expressing cells, wherein said immunoconjugate is administered 1-6 hours after completion of the administration of said unconjugated antibody.

A method for treating a disease associated with target cells expressing CD138 comprising:

• administering to a subject in need thereof an immunoconjugate comprising at least one engineered targeting antibody targeting CD138 expressing cells, and
• at least one maytansinoid, wherein said engineered targeting antibody is functionally attached to said maytansinoid to form said immunoconjugate, wherein at least a part of the engineered targeting antibody confers IgG4 isotype properties, and
• wherein the immunoconjugate is administered in a multiple dose regimen comprising
• three doses within 21days, being administered once a week about 9.28 mg/m2 or 11.4 mg/m2 to about 25.7 mg/m2, or more than three doses administered more than once a week and corresponding to a daily dose of about 9.28 mg/m2 or 11.4 mg/m2 to about 25.7 mg/m2, followed by a resting period of about one week, which together define a treatment cycle of at least 28 days and administering at least one cytotoxic agent, including two or three, at least once a week or once in a treatment cycle.