Date: 2013-12-10
Type of information: Presentation of results at a congress
phase: 1-2a
Announcement: presentation of results at the 55th Annual meeting of the American Society of Hematology (ASH) in New Orleans.
Company: Biotest (Germany)
Product: indatuximab ravtansine (BT-062)
Action
mechanism: antibody drug conjugate (ADC). Indatuximab ravtansine (BT-062) is an antibody-drug conjugate consisting of a monoclonal antibody and a highly potent cytotoxic maytansine derivative (DM4). The antibody binds specifically to the antigen CD138, which is over-expressed on multiple myeloma cells and a variety of solid tumors. Once the conjugate is internalized into the target cell, the DM4 is released from the targeting molecule, thereby restoring its original cytotoxic potency.
Disease: multiple myeloma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This phase I/IIa trial (Study No. 983) is designed to evaluate indatuximab ravtansine (BT-062) (administered days 1, 8 and 15, every 4 weeks) when used in combination with lenalidomide/dexamethasone to treat patients with relapsed or relapsed/refractory multiple myeloma. To qualify for enrollment, patients must have received at least one prior treatment regimen, which could include lenalidomide and/or dexamethasone. In the phase I part of the trial, patients were administered increasing doses of indatuximab ravtansine (BT-062) to determine its MTD when used in combination with lenalidomide and dexamethasone. In the Phase IIa part, indatuximab ravtansine (BT-062) is being administered at its MTD to further assess its safety and efficacy in combination with lenalidomide/dexamethasone. (NCT01001442)
Latest
news: * On December 10, 2013. Biotest AG has announced that new clinical data derived from an ongoing combination study with indatuximab ravtansine (BT-062) were discussed in an oral presentation at the 55th Annual meeting of the American Society of Hematology (ASH) in New Orleans. The phase I/IIa study (Study 983) is investigating the safety and efficacy of indatuximab ravtansine (BT-062) in combination with lenalidomide and dexamethasone in patients with relapsed (recurring) or relapsed/refractory (resistent) multiple myeloma. These data will be the basis for further clinical development of indatuximab ravtansine (BT-062) in multiple myeloma.In Study 983, to date 21 patients were treated with indatuximab ravtansine (BT-062) on days 1, 8, and 15 in combination with lenalidomide and dexamethasone in a 4-week cycle. Treatment cycles were repeated until progression of the underlying disease or occurrence of unacceptable toxicities. To be eligible for enrollment, patients must have relapsed or relapsed/refractory multiple myeloma; patient could previously have been treated with lenalidomide and/or dexamethasone. In the Phase I portion of the trial, three different doses of indatuximab ravtansine (BT-062) - 80, 100, 120 mg/m2 - were evaluated in combination with lenalidomide and dexamethasone to establish the maximum tolerated dose (MTD) of BT-062 when used with these drugs. indatuximab ravtansine (BT-062) was then evaluated at its MTD (100 mg/m2), with lenalidomide/ dexamethasone in additional patients.The available data indicate that indatuximab ravtansine (BT-062) is well tolerated in the combination regimen at doses of up to 100 mg/m² (MTD). Efficacy was evaluated based on patients for whom at least two efficacy assessments after start of treatment were available. Preliminary efficacy evaluation from 15 patients across all dose levels reveals that 100 % of the heavily pretreated patients had clinical benefit from the therapy, achieving stable disease or better. Eleven of these patients achieved a partial up to a complete response, resulting in an objective response rate of 73%. A comparable objective response rate of 75% was also obtained in a subgroup of patients who were refractory to prior therapy with lenalidomide and dexamethasone. For eight out of nine evaluated patients treated at the MTD of 100 mg/m², partial response or better with an objective response rate of 89% was observed. At this phase II dose level of 100 mg/m² (MTD) a total of 37 patients will be treated to further evaluate the safety and efficacy in a larger number of patients.These data will be the basis for further clinical development of indatuximab ravtansine (BT-062) in multiple myeloma.* On July 16, 2012, Biotest AG is pursuing an innovative therapeutic strategy to treat multiple myeloma using the antibody-drug conjugate (ADC) BT-062. BT-062 is currently in clinical development for treating patients with relapsed or relapsed/refractory multiple myeloma. Two clinical trials investigating different dose schedules of BT-062 as monotherapy have shown good tolerability and have provided evidence for anti-tumor activity.Whereas treatment of 32 patients within the first monotherapy study 969 is finished, Biotest continues to investigate BT-062 as monotherapy in study 975. In study 975 about 50 patients with relapsed or relapsed/refractory multiple will be treated at a more frequent dose schedule, receiving intravenous administration of BT-062 on days 1, 8, and 15 every 4 weeks. The patient recruitment of the first seven dose levels has been completed. So far BT-062 continued to be well tolerated. In addition, initial evidence of efficacy was confirmed. Currently, Biotest expands the clinical development of BT-062 into combination therapy. The phase I/IIa study (study no. 983) investigates safety and efficacy of BT-062 when administered on days 1, 8, and 15 every 4 weeks in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. A few days ago the first patient in study 983 started treatment. Biotest will continue to focus its resources on the development of BT-062 in the lead indication multiple myeloma.* On December 12, 2011, Biotest AG has announced that new clinical data with BT-062 in the indication multiple myeloma were featured in an oral presentation at the 53rd annual meeting of the American Society of Hematology (ASH) in San Diego. The clinical data were obtained from two ongoing studies assessing BT-062 as monotherapy: A phase I repeated single-dose trial (study no. 969) and a phase I/IIa multiple-dose trial (study no. 975). In both trials, patients suffering from multiple myeloma receive repeated treatments with BT-062 until progression of the underlying disease or occurrence of unacceptable toxicities.In study 969, 32 patients with relapsed or relapsed/refractory multiple myeloma were treated with BT-062 administered once every three weeks. Preliminary findings reveal that more than 50 % of the treated, heavily pretreated patients benefited from the therapy. Among these is a patient who achieved a sustained clinical benefit for more than one and a half years and is still under treatment with BT-062. Data show that BT-062 is well tolerated at doses of up to 160 mg/m², even when administered over a long treatment period of currently 26 treatment cycles. Based on these results study 975 is underway to treat about 50 patients with relapsed or relapsed/refractory multiple myeloma in an intensified dose schedule. BT-062 is given on days 1, 8 and 15 of 4-week cycle. At the first 5 dose levels of up to 100 mg/m² per dose tested so far, BT-062 was well tolerated and initial evidence of efficacy was observed. To date, no dose limiting toxicities have been observed and escalation towards higher doses is ongoing. Based on the promising clinical results from these two monotherapy studies and supported by the preclinical combination studies, Biotest will submit its first clinical BT-062 combination study in multiple myeloma to the FDA. The phase I/IIa study (study no. 983) will investigate BT-062 in combination with lenalidomide and dexamethasone in relapsed or relapsed/refractory patients.
