Date: 2016-06-06
Type of information: Presentation of results at a congress
phase: 1-2a
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: MorphoSys (Germany)
Product: MOR202 (antiCD38 antibody)
Action
mechanism: monoclonal antibody. MOR202 is a fully human HuCAL antibody directed against CD38, a therapeutic target which is highly expressed on multiple myeloma tumor cells and certain leukemias.
Disease: relapsed or refractory multiple myeloma
Therapeutic area: Cancer - Oncology - Rare diseases
Country: Austria, Germany
Trial
details: The ongoing phase 1/2a, open-label, multi-center, dose-escalation study is being conducted in several centers in Germany and Austria. The study is evaluating the safety and preliminary efficacy of MOR202 as monotherapy and in combination with pomalidomide and lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma. The primary endpoints of the trial are the safety, tolerability and recommended dose of MOR202 alone and in combination with immunomodulatory drugs (IMiDs). Secondary outcome measures are pharmacokinetics and preliminary efficacy based on overall response rate, duration of response, time-to-progression, and progression-free survival. (NCT01421186 )
Latest
news: * On June 6, 2016, MorphoSys has presented updated clinical data for MOR202 in multiple myeloma at ASCO 2016. The company has presented updated safety and efficacy data from an ongoing clinical phase 1/2a study evaluating the anti-CD38 antibody MOR202 alone and in combination with immunomodulatory drugs (IMiDs) lenalidomide (Len) and pomalidomide (Pom) plus dexamethasone (Dex) in 63 heavily pre-treated patients with relapsed/refractory multiple myeloma (MM). Data were reported during a poster presentation at the 2016 ASCO Annual Meeting. The updates compared to the last presentation of data from this ongoing trial in December 2015 refer in particular to the combination cohorts of MOR202 (8 mg/kg) plus IMiDs. * On November 5, 2015, MorphoSys announced presentations of data on the Company's proprietary programs at the 57th American Society of Hematology (ASH) Annual Meeting, being held December 5-8, 2015 in Orlando, Florida. Presentations included updated safety and efficacy results from the ongoing MOR202 dose-escalation study in multiple myeloma patients (Phase I/IIa Study of the Human Anti-CD38 Antibody MOR202 (MOR03087) in Relapsed or Refractory Multiple Myeloma), data from the highest dose cohort of MOR202 as monotherapy, as well as from the first two cohorts of patients receiving MOR202 in combination with lenalidomide and pomalidomide. * On September 23, 2015, MorphoSys published updated safety and preliminary efficacy data on MOR202 from an ongoing phase 1/2a study. The clinical data presented at the 15th International Myeloma Workshop in Rome, Italy, September 23th-26th, confirm the very good overall safety profile previously reported at this year's ASCO meeting. The update also includes promising first results from the highest dose escalation cohort of 16 mg/kg of MOR202 weekly plus dexamethasone and from the recently initiated combination arms with the immunomodulatory drugs (IMiDs) pomalidomide and lenalidomide. As of August 24, 2015, 50 heavily pretreated patients with relapsed/refractory multiple myeloma had received MOR202 with and without dexamethasone and in a few cases in combination with pomalidomide or lenalidomide as part of a recently initiated second part of the study. MOR202 continued to demonstrate long-lasting tumor control, as well as signs of activity. In addition to the earlier reported very good partial response (VGPR) in a cohort dosed weekly with 4 mg/kg of MOR202 plus dexamethasone, a minor response (MR) in the 8 mg/kg MOR202 weekly plus dexamethasone cohort further improved into a partial response (PR). A first MR was observed in one patient in an ongoing cohort at the highest dose level, of 16 mg/kg MOR202 plus dexamethasone. The first evaluable patient in the ongoing combination cohort of 8 mg/kg MOR202 plus pomalidomide and dexamethasone achieved a PR already after the first cycle. In the ongoing combination cohort of 8 mg/kg MOR202 plus lenalidomide and dexamethasone, one patient showed a MR after the first cycle. In total, the data shows one VGPR, two PRs and two MRs so far. The data show that MOR202 was safe and tolerable and could be administered as a 2-hour infusion. Infusion-related reactions occurred in 15 patients (30%). Only one out of these 15 patients received dexamethasone as co-medication and experienced an infusion-related reaction (grade 1). In the absence of dexamethasone, all infusion reactions were grade 1-2 except for one patient with grade 3, mainly limited to the first infusion. The maximum tolerated dose has not been reached. * On May 31, 2015, MorphoSys published first safety and efficacy data on MOR202. The data are from a phase 1/2a study in 42 heavily pretreated patients with relapsed/refractory multiple myeloma. The preliminary clinical data, which were presented at the 2015 American Society of Clinical Oncology Annual Meeting (ASCO), show that MOR202 was safe and well tolerated with a best-in-class infusion tolerability as a 2-hour infusion. Infusion reactions in patients receiving MOR202 without dexamethasone were mostly mild to moderate and mainly limited to the first infusion. In patients receiving MOR202 in combination with dexamethasone, no infusion reactions were observed. MOR202 demonstrated promising early signs of activity, and cases of long-lasting tumor control were already observed in early cohorts. The data presented at the ASCO 2015 meeting show that MOR202 was safe and tolerable and could be administered as a 2-hour infusion. Infusion-related reactions occurred in 13 patients (37%) receiving MOR202 without dexamethasone, mainly limited to the first infusion. All infusion reactions were grade 1-2 except for one patient with grade 3. No infusion reactions occurred in patients who received dexamethasone. The maximum tolerated dose (MTD) has not been reached. The best response to date, a very good partial response (VGPR), was achieved in the 4.0 mg/kg weekly dose cohort plus dexamethasone. Additionally, one minimal response (MR) and ten cases of stable disease (SD) in other dose groups starting as low as 1.5 mg/kg biweekly were reported. The preliminary pharmacokinetic data indicate the potential for full target occupancy with a dose of 16 mg/kg administered weekly. The study is ongoing and the higher doses of MOR202 are being evaluated in combination with dexamethasone. Further cohorts in which patients will receive MOR202 up to 16 mg/kg weekly in combination with the IMiDs pomalidomide and lenalidomide plus dexamethasone will commence shortly. MorphoSys additionally presented preclinical data demonstrating the synergistic potential of MOR202 and pomalidomide, an established immunomodulatory agent in relapsed/refractory multiple myeloma therapy. This synergistic benefit was between 1.2-fold and 3.1-fold above the theoretical benefit of combining the drugs and resulted from multiple mechanisms, namely direct cytotoxicity, CD38 up-regulation and activation of effector cells. * On July 28, 2014, MorphoSys provided an update on its proprietary portfolio including the clinical programs MOR208, MOR103 and MOR202. As these programs progress through clinical development, the company continually aims to strengthen its proprietary portfolio through new program starts, co-development and in-licensing agreements and potentially through M&A transactions. MorphoSys and its collaboration partner Celgene Corporation have decided to expand the clinical development plan of MOR202 in multiple myeloma, introducing pomalidomide as a new combination partner. The MOR202 combination trials are now planned to be initiated earlier than originally anticipated. In addition, cohorts with a weekly dosing schedule, with and without dexamethasone, were added to the ongoing monotherapy trial of MOR202, which continues as planned. The expanded design of the trial will be published on www.clinicaltrials.gov. As the now expanded Phase 1/2a trial will not be completed until 2015, the companies do not plan to publish any clinical data this year. * On September 1, 2011, MorphoSys has announced that the first patient in a Phase 1/2a clinical trial of its cancer antibody MOR202 has been dosed. The phase 1/2a, open-label, multi-centre, dose-escalation study will evaluate the safety and preliminary efficacy of MOR202 in patients with relapsed or refractory multiple myeloma. Patients with relapsed or refractory multiple myeloma will be treated with different doses of the HuCAL-derived antibody MOR202. It is also planned to evaluate the safety of MOR202 in combination with approved therapy. Pre-clinical studies recently presented at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO) demonstrated enhanced cytotoxic activity of MOR202 in combination with Velcade® and Revlimid®, supporting the clinical trial design.
In the five-patient cohort receiving 8 mg/kg MOR202 in combination with Pom/Dex, two patients reached a complete response (CR) and two patients a minor response (MR) (one of which is unconfirmed). Among the four patients treated with 8 mg/kg MOR202 in combination with Len/Dex and with a scheduled response assessment after one treatment cycle, two reached a partial response (PR) and one a very good partial response (VGPR).
MOR202 could be given in doses of up to 16 mg/kg as a 2-hour infusion to all patients. Infusion-related reactions (IRRs) were observed in 14% of evaluated patients (10% grade 1, 4% grade 2) and were mainly limited to the first infusion.
Moreover, first biomarker data on CD38 expression on plasma cells derived from bone marrow of all five MM patients with available second biopsies, suggested that the CD38 target molecule was preserved during MOR202 therapy comparing values at baseline and at cycle 2 day1. "Since we last reported data in December 2015, new and deep responses have been reported with MOR202 in combination with IMiDs. On the safety side, we were pleased to observe that MOR202 could be given to all patients in a 2-hour infusion time, with infusion-related reactions of grade 1 and 2 in only 14% of patients," commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG. "The dose escalation study will continue as planned, focusing on the combination treatment, in particular the upcoming cohorts of 16mg/kg MOR202 plus Pom/Dex and Len/Dex."
