On June 6, 2016 Merck KGaA, Darmstadt, Germany, and Pfizer (NYSE: PFE) reported results from the first pivotal, international, multicenter, open-label, Phase II study of avelumab*, which showed a 31.8% objective response rate (ORR) (28 of 88 patients; 95.9% CI: 21.9–43.1%†), in the pre-planned primary analysis of the study, and a manageable safety profile in patients with metastatic Merkel cell carcinoma (MCC) who were treated with avelumab in second or subsequent lines of therapy (Press release, Pfizer, JUN 6, 2016, View Source [SID:1234513077]). Tumor responses were rapid, with 78.6% of patients (22 of 28) responding within 7 weeks of starting treatment, and durable, with 82.1% of patients (23 of 28) still responding at the time of analysis. No unexpected safety signals were reported. These data will be reported today during an oral presentation at the 52nd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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"To see a tumor response in almost a third of patients in this trial, and for the majority to keep responding after six months, represents a potential breakthrough for this challenging disease," said lead investigator Howard L. Kaufman, M.D., FACS, Rutgers Cancer Institute of New Jersey, USA. "Currently, the only treatment option available for advanced stages of this aggressive type of skin cancer is chemotherapy, where the response rates are not adequate or durable."

Metastatic MCC has a poor prognosis with less than 20% of patients surviving longer than five years.1 Although chemotherapy is considered a second-line treatment option for metastatic MCC, it is not a standard of care. Current guidelines recommend that these patients participate in clinical trials.2

"This is an important milestone for us as this is the largest data set of any anti-PD-L1 or anti-PD-1 reported to date in this patient population," said Luciano Rossetti, Executive Vice President, Global Head of Research & Development in the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "The clinically meaningful tumor response rate for avelumab in metastatic Merkel cell carcinoma where chemotherapy has failed, reinforces our belief in the promise of this molecule, particularly considering the high unmet need in this disease."

In the trial, eight patients (9.1%) achieved complete responses and 20 patients (22.7%) achieved partial responses. The median duration of response has not been reached (95% CI: 8.3 months – not estimable; range, 2.8–17.5+ months). Tumor responses were seen in patients regardless of the status of certain biomarkers (PD-L1 and Merkel cell polyomavirus). The progression-free survival (PFS) rate at 6 months was 40% (95% CI: 29–50%, estimated by the Kaplan-Meier method). Early data also showed an overall survival (OS) rate at 6 months of 69% (95% CI: 58–78%) and a median OS of 11.3 months (7.5–14.0 months); however, these OS data are still maturing since minimum follow-up was 6 months for inclusion in this analysis. Treatment-related adverse events (AEs) occurred in 62 patients (70.5%); the most common were fatigue (23.9%) and infusion-related reactions (17.0%), all of which were Grade 1 or 2. Grade 3 treatment-related AEs were reported in four patients (4.5%). There were no Grade 4 treatment-related AEs or deaths.

"This has been an exciting ASCO (Free ASCO Whitepaper) for the strategic collaboration between the two companies, between the MCC data and the other encouraging responses observed across a broad range of tumors," said Chris Boshoff, M.D., PhD., Vice President and Head of Early Development, Translational and Immuno-Oncology at Pfizer Oncology. "The clinical benefits for avelumab as a monotherapy in notably hard-to-treat cancers may be amplified even further when combined with other therapies."

Avelumab has received multiple regulatory designations in MCC from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), including Orphan Drug (FDA and EMA), Fast Track and Breakthrough status (FDA). There are plans to submit marketing applications for avelumab to regulatory authorities based on these data.

About JAVELIN Merkel 200

JAVELIN Merkel 200 is an international, multicenter, open-label, Phase II study of avelumab conducted in 88 patients with metastatic MCC. Patients in this study were generally elderly (median age was 72.5 years, range 33–88 years) and pre-treated, with at least one line of chemotherapy (one [59.1%], two [29.5%] or three or more [11.4%] previous treatments). Patients received avelumab 10 mg/kg intravenously once every two weeks. The protocol-defined analysis set for efficacy and safety consisted of all patients who received at least one dose of study treatment. The cut-off date for the planned primary analysis was 6 months after start of study treatment of the last patient. The primary endpoint of the study was confirmed best overall response according to RECIST v1.1 and assessed by an independent review committee. Secondary endpoints were duration of response, PFS, OS, response status by RECIST at 6 and 12 months, safety and tolerability, pharmacokinetics, and immunogenicity of avelumab.

*Avelumab is the proposed nonproprietary name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

†Multiplicity adjustment accounting for interim analysis to achieve overall 95% confidence level.

References

Lemos B, Storer B, Iyer J, et al. Pathologic Nodal Evaluation Improves Prognostic Accuracy in Merkel Cell Carcinoma: Analysis of 5,823 Cases as the Basis of the First Consensus Staging System for this Cancer. Journal of the American Academy of Dermatology. 2010;63:751-761.
NCCN Merkel Cell Carcinoma Guidelines Version I. 2016. Available from: www.nccn.org/professionals/physician_gls/PDF/mcc.pdf (link is external). Accessed April 2016.
About Avelumab

Avelumab (also known as MSB0010718C) is an investigational, fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an investigational anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.

About Merck KGaA, Darmstadt, Germany

All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe (link is external) to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2015, Merck KGaA, Darmstadt, Germany, generated sales of € 12.85 billion in 66 countries.

Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world’s oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany operates as EMD Serono, MilliporeSigma and EMD Performance Materials in the United States and Canada.

On June 6, 2016 Merck KGaA, Darmstadt, Germany, and Pfizer (NYSE: PFE) reported results from the first pivotal, international, multicenter, open-label, Phase II study of avelumab*, which showed a 31.8% objective response rate (ORR) (28 of 88 patients; 95.9% CI: 21.9–43.1%†), in the pre-planned primary analysis of the study, and a manageable safety profile in patients with metastatic Merkel cell carcinoma (MCC) who were treated with avelumab in second or subsequent lines of therapy (Press release, Pfizer, JUN 6, 2016, View Source [SID:1234513076]). Tumor responses were rapid, with 78.6% of patients (22 of 28) responding within 7 weeks of starting treatment, and durable, with 82.1% of patients (23 of 28) still responding at the time of analysis. No unexpected safety signals were reported. These data will be reported today during an oral presentation at the 52nd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"To see a tumor response in almost a third of patients in this trial, and for the majority to keep responding after six months, represents a potential breakthrough for this challenging disease," said lead investigator Howard L. Kaufman, M.D., FACS, Rutgers Cancer Institute of New Jersey, USA. "Currently, the only treatment option available for advanced stages of this aggressive type of skin cancer is chemotherapy, where the response rates are not adequate or durable."

Metastatic MCC has a poor prognosis with less than 20% of patients surviving longer than five years.1 Although chemotherapy is considered a second-line treatment option for metastatic MCC, it is not a standard of care. Current guidelines recommend that these patients participate in clinical trials.2

"This is an important milestone for us as this is the largest data set of any anti-PD-L1 or anti-PD-1 reported to date in this patient population," said Luciano Rossetti, Executive Vice President, Global Head of Research & Development in the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "The clinically meaningful tumor response rate for avelumab in metastatic Merkel cell carcinoma where chemotherapy has failed, reinforces our belief in the promise of this molecule, particularly considering the high unmet need in this disease."

In the trial, eight patients (9.1%) achieved complete responses and 20 patients (22.7%) achieved partial responses. The median duration of response has not been reached (95% CI: 8.3 months – not estimable; range, 2.8–17.5+ months). Tumor responses were seen in patients regardless of the status of certain biomarkers (PD-L1 and Merkel cell polyomavirus). The progression-free survival (PFS) rate at 6 months was 40% (95% CI: 29–50%, estimated by the Kaplan-Meier method). Early data also showed an overall survival (OS) rate at 6 months of 69% (95% CI: 58–78%) and a median OS of 11.3 months (7.5–14.0 months); however, these OS data are still maturing since minimum follow-up was 6 months for inclusion in this analysis. Treatment-related adverse events (AEs) occurred in 62 patients (70.5%); the most common were fatigue (23.9%) and infusion-related reactions (17.0%), all of which were Grade 1 or 2. Grade 3 treatment-related AEs were reported in four patients (4.5%). There were no Grade 4 treatment-related AEs or deaths.

"This has been an exciting ASCO (Free ASCO Whitepaper) for the strategic collaboration between the two companies, between the MCC data and the other encouraging responses observed across a broad range of tumors," said Chris Boshoff, M.D., PhD., Vice President and Head of Early Development, Translational and Immuno-Oncology at Pfizer Oncology. "The clinical benefits for avelumab as a monotherapy in notably hard-to-treat cancers may be amplified even further when combined with other therapies."

Avelumab has received multiple regulatory designations in MCC from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), including Orphan Drug (FDA and EMA), Fast Track and Breakthrough status (FDA). There are plans to submit marketing applications for avelumab to regulatory authorities based on these data.

About JAVELIN Merkel 200

JAVELIN Merkel 200 is an international, multicenter, open-label, Phase II study of avelumab conducted in 88 patients with metastatic MCC. Patients in this study were generally elderly (median age was 72.5 years, range 33–88 years) and pre-treated, with at least one line of chemotherapy (one [59.1%], two [29.5%] or three or more [11.4%] previous treatments). Patients received avelumab 10 mg/kg intravenously once every two weeks. The protocol-defined analysis set for efficacy and safety consisted of all patients who received at least one dose of study treatment. The cut-off date for the planned primary analysis was 6 months after start of study treatment of the last patient. The primary endpoint of the study was confirmed best overall response according to RECIST v1.1 and assessed by an independent review committee. Secondary endpoints were duration of response, PFS, OS, response status by RECIST at 6 and 12 months, safety and tolerability, pharmacokinetics, and immunogenicity of avelumab.

*Avelumab is the proposed nonproprietary name for the anti-PD-L1 monoclonal antibody (MSB0010718C). Avelumab is under clinical investigation and has not been proven to be safe and effective. There is no guarantee any product will be approved in the sought-after indication by any health authority worldwide.

†Multiplicity adjustment accounting for interim analysis to achieve overall 95% confidence level.

References

Lemos B, Storer B, Iyer J, et al. Pathologic Nodal Evaluation Improves Prognostic Accuracy in Merkel Cell Carcinoma: Analysis of 5,823 Cases as the Basis of the First Consensus Staging System for this Cancer. Journal of the American Academy of Dermatology. 2010;63:751-761.
NCCN Merkel Cell Carcinoma Guidelines Version I. 2016. Available from: www.nccn.org/professionals/physician_gls/PDF/mcc.pdf (link is external). Accessed April 2016.
About Avelumab

Avelumab (also known as MSB0010718C) is an investigational, fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and the adaptive immune system. By retaining a native Fc-region, avelumab is thought to potentially engage the innate immune system and induce antibody-dependent cell-mediated cytotoxicity (ADCC). In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an investigational anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.

About Merck KGaA, Darmstadt, Germany

All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe (link is external) to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2015, Merck KGaA, Darmstadt, Germany, generated sales of € 12.85 billion in 66 countries.

Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world’s oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany operates as EMD Serono, MilliporeSigma and EMD Performance Materials in the United States and Canada.

On June 6, 2016 Nektar Therapeutics (NASDAQ: NKTR) reported new preclinical data for NKTR-214, an immuno-stimulatory CD-122 biased cytokine currently being evaluated in cancer patients with solid tumors in a Phase 1/2 clinical trial being conducted at MD Anderson Cancer Center and Yale Cancer Center (Press release, Nektar Therapeutics, JUN 6, 2016, View Source [SID:1234513074]). The new preclinical data presented demonstrate that treatment with single-agent NKTR-214 mobilizes tumor-killing T cells into colon cancer tumors. In addition, mouse pharmacodynamics data demonstrated that a single dose of NKTR-214 can increase and sustain STAT5 phosphorylation (a marker of IL-2 pathway activation) through one week post-dose. These data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL from June 3-7, 2016.

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"These latest data build upon our growing body of preclinical evidence demonstrating the unique mechanism of NKTR-214," added Jonathan Zalevsky, PhD, Vice President, Biology and Preclinical Development at Nektar Therapeutics. "The studies presented at ASCO (Free ASCO Whitepaper) show that NKTR-214 promotes tumor-killing immune cell accumulation directly in the tumor, providing a mechanistic basis for its significant anti-tumor activity in multiple preclinical tumor models. The ability to grow TILs1 in vivo and replenish the immune system is exceptionally important. We’ve now learned that many human tumors lack sufficient TIL populations and the addition of the NKTR-214 TIL-enhancing MOA could improve the success of many checkpoint inhibitors and other agents, and allow more patients to benefit from immuno-therapy."

In studies previously published for NKTR-214, when mice bearing established breast cancer tumors are treated with NKTR-214 and anti-CTLA4 (a checkpoint inhibitor therapy known as ipilimumab for human treatment), a large proportion of mice become tumor-free. Anti-tumor immune memory was demonstrated when tumor-free mice were re-challenged by implant with a new breast cancer tumor and then found to clear the new tumor, without further therapy. The new data presented at ASCO (Free ASCO Whitepaper) demonstrate that upon re-challenge, there is a rapid expansion of newly proliferative CD8 T cells and particularly CD8 effector memory T cells. Both cell populations were readily detectable in multiple tissues (blood, spleen, and lymph nodes) and likely contribute to the anti-tumor effect observed in these animals. Adoptive transfer studies confirmed the immune-memory effect as transplant of splenocytes from tumor-free mice into naïve recipients provided the ability to resist tumor growth.

"NKTR-214 provides a highly unique immune activation profile that allows it to access the IL-2 pathway without pushing the immune system into pathological overdrive," said Dr. Steve Doberstein, Senior Vice President and Chief Scientific Officer. "NKTR-214’s unique immune-stimulatory profile and antibody-like dosing schedule positions it as a potentially important medicine within the immuno-oncology landscape."

The data presentation at ASCO (Free ASCO Whitepaper) entitled, "Immune memory in nonclinical models after treatment with NKTR-214, an engineered cytokine biased towards expansion of CD8+ T cells in tumor," can be accessed at View Source

NKTR-214 is a CD122-biased agonist designed to stimulate the patient’s own immune system to kill tumor cells by preferentially activating production of specific immune cells which promote tumor killing, including CD8-positive T cells and Natural Killer (NK) cells, within the tumor micro-environment. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these types of T cells.2

In preclinical studies, NKTR-214 demonstrated a highly favorable mean ratio of 450:1 within the tumor micro-environment of CD8-positive effector T cells relative to regulatory T cells.3 Furthermore, the pro-drug design of NKTR-214 enables an antibody-like dosing regimen for an immuno-stimulatory cytokine.4

About the NKTR-214 Phase 1/2 Clinical Study
A Phase 1/2 clinical study is underway to evaluate NKTR-214 in patients with advanced solid tumors, including melanoma, renal cell carcinoma and non-small cell lung cancer. The first stage of this study, which is expected to be complete in the second half of 2016, is evaluating escalating doses of single-agent NKTR-214 treatment in approximately 20 patients with solid tumors. The primary objective of the first stage of the study is to evaluate the safety and efficacy of NKTR-214 and to identify a recommended Phase 2 dose. In addition, the study will also assess the immunologic effect of NKTR-214 on TILs and other immune cells in both blood and tumor tissue, and it will also include TCR repertoire profiling. Dose expansion cohorts are planned to evaluate NKTR-214 in specific tumor types, including melanoma, renal cell carcinoma and non-small cell lung cancer.

The NKTR-214 clinical study is being conducted initially at two primary investigator sites: MD Anderson Cancer Center under Drs. Patrick Hwu and Adi Diab; and Yale Cancer Center, under Drs. Mario Sznol and Michael Hurwitz. Patients and physicians interested in the ongoing NKTR-214 study can visit the "Clinical Trials" section of www.mdanderson.org using identifier 2015-0573 or visit View Source

On June 6, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported 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) (Press release, MorphoSys, JUN 6, 2016, View Source [SID:1234513073]). Data were reported during a poster presentation at the 2016 ASCO (Free ASCO Whitepaper) 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.

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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.

"We are very pleased with the updated clinical results for MOR202 in multiple myeloma, in particular with two complete responses out of five patients treated with MOR202 plus Pom/Dex. 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."

MOR202 is a fully human HuCAL antibody targeting CD38, a highly expressed and validated target in multiple myeloma. Data are from an ongoing clinical phase 1/2a, open-label, multi-center, dose-escalation study conducted in several sites in Germany and Austria. The study is evaluating the safety and preliminary efficacy of MOR202 alone and in combination with the immunomodulatory drugs pomalidomide (Pom) and lenalidomide (Len) plus dexamethasone (Dex) 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 the IMiDs. Secondary outcome measures are pharmacokinetics and preliminary efficacy based on overall response rate, duration of response, time-to-progression, and progression-free survival.

MOR208: Updated results confirm responses. Subgroup analysis shows target lesion shrinkage in patients with stable disease and activity of MOR208 independent of the response to a prior rituximab treatment

In addition, MorphoSys today presented updated clinical data including a subgroup analysis of a phase 2a study with the anti-CD19 antibody MOR208 in relapsed/refractory patients with various subtypes of non-Hodgkin’s lymphoma (NHL) including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and other indolent NHL (iNHL). All patients had received at least one prior rituximab-containing therapy.

According to the subgroup analysis data presented today, in addition to patients achieving a partial or complete response (PR, CR), a clinical benefit was also observed in other patients treated with MOR208. The majority of patients (5/6 DLBCL and 12/16 iNHL) with stable disease (SD) also had a reduction in the size of the target lesions – despite the short treatment period of 3 cycles according to protocol. This resulted in a disease control rate of 40% in DLBCL and 73% in iNHL patients. Moreover, progression-free survival (PFS) with MOR208 therapy was observed to be comparable in rituximab refractory and non-refractory NHL patients (median PFS 5.3 versus 6.6 months, HR 0.85, 95% CI 0.45-1.6, p=0.59). Thus, MOR208 has demonstrated in this trial activity independent of the response to a prior anti-CD20 therapy. Updated data for the overall trial population furthermore revealed that after 12 months the PFS rate was 40% in both DLBCL and iNHL patients. Nine patients treated with MOR208 are still in remission (7 CRs, 2 PRs), the longest responses currently ongoing for 26 months.

"We are very happy with the updated clinical trial results with MOR208," commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG. "We are impressed by the duration of responses of up to 26 months with MOR208 as a single-agent in heavily pre-treated patients with relapsed/refractory NHL. We were further pleased to observe a decline in the size of the tumor lesions in many in the subgroup of patients with stable disease even when treated for a short period of 3 cycles only. Overall, the updated clinical data presented at ASCO (Free ASCO Whitepaper) strongly support our strategy to develop MOR208 in B cell malignancies, in particular our planned combination trials in DLBCL and CLL."

MOR208 is an anti-CD19 antibody with a proprietary modification to the Fc portion in clinical development to treat B cell malignancies. The open-label, phase 2a, multicenter study was designed to assess the activity and safety of weekly doses of 12 mg/kg MOR208 as a single agent in 92 pre-treated patients with various subtypes of relapsed/refractory NHL patients. According to the data observed, MOR208 showed a low level of infusion reactions. The overall response rate (ORR) of MOR208 reached 36% in the DLBCL subgroup and 33% in iNHL patients (both based on evaluable patients). Based on all patients with DLBCL and iNHL in the study, the ORR was 26% and 29%, respectively.

In addition, the trial design of a phase 2 study of MOR208 (COSMOS trial) was presented at the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting. The trial is planned to evaluate MOR208 in combination with idelalisib in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), in patients no longer responding to or no longer tolerating Bruton’s tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib). After the discontinuation of several combination trials of idelalisib with other compounds, this planned trial is currently under review and discussions with regulatory authorities are ongoing. MorphoSys is currently exploring alternative study designs to evaluate MOR208 in a combination trial in CLL/SLL patients previously treated with a BTK inhibitor.

The posters presented at the Annual ASCO (Free ASCO Whitepaper) Meeting, June 6, 2016, 8:30 am CDT (2:30 pm BST, 3:30 pm CEST), can be downloaded from the Company’s website.

Abstract #8012
M. Raab et al: MOR202 alone and in combination with pomalidomide or lenalidomide in relapsed or refractory multiple myeloma: Data from clinically relevant cohorts from a phase 1/2a study.

Abstract #7545
W. Jurczak et al: Subgroup analyses of diffuse large B-cell lymphoma (DLBCL) and indolent lymphoma cohorts from a phase 2a study of single-agent MOR208 in patients with relapsed or refractory non-Hodgkin’s lymphoma (R-R NHL).

Abstract #TPS7572
C.-M. Wendtner et al: A phase 2 study of MOR208 plus idelalisib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a Bruton’s tyrosine kinase inhibitor.

MorphoSys will hold on June 6, 2016 at 6:30 p.m. CDT (June 7, 2016 0:30 a.m. BST, 1:30 a.m. CEST) an Investor & Analyst Event at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting. KOLs will present the new clinical data for MOR208 and MOR202. A replay and the presentation will be made available at View Source Live-Webcast: http://morphosys.equisolvewebcast.com/investor-event-6-6-16

On June 6, 2016 Mirna Therapeutics, Inc. (Nasdaq: MIRN), a clinical stage biopharmaceutical company developing a broad pipeline of microRNA-based oncology therapeutics, reported the presentation of clinical data at the 52nd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Mirna Therapeutics, JUN 6, 2016, View Source [SID:1234513072]). Investigators reported on the clinical activity of an ongoing, dose-finding Phase 1 trial of MRX34 (miR-34 mimic), Mirna’s lead microRNA therapeutic, in patients with a variety of advanced solid tumors.

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In an oral presentation (Abstract # 2508 "MRX34, a Liposomal miR-34 Mimic, in Patients with Advanced Solid Tumors: Final Dose-Escalation Results from a First-in-Human Phase 1 Trial of microRNA Therapy"), David S. Hong, M.D., study author and Deputy Chair, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, presented results showing MRX34’s impact on a broad number of oncogenes and immune pathways, and on the investigational therapy’s safety profile and clinical activity.

"The potential of microRNA therapeutics to simultaneously repress multiple oncogenic and immune-evasion pathways represents an exciting new approach to treating cancer," commented Dr. Hong. "In this early study, we are seeing compelling anti-cancer activity, including tumor shrinkage with notable durations of response, supporting further clinical study of MRX34."

Data highlights include:

Manageable safety profile of MRX34 when administered at the maximum tolerated dose (MTD) with dexamethasone.
Broad, dose-dependent microRNA target engagement with MRX34, including delivery to tumor sites in patients.
Four confirmed partial responses (PRs) for up to 54 weeks in duration. This includes patients with late-stage, metastatic cancers including hepatocellular carcinoma (liver cancer), renal cell carcinoma (kidney cancer) and acral melanoma (skin cancer). Timing of these responses and the safety profile observed suggest a potential immune component to MRX34 antitumor activity.
Stable disease in an additional 15 patients for more than four cycles of therapy (approximately three months), ranging from 79-386 days.
Vincent O’Neill, M.D., Mirna’s Chief Medical Officer commented, "We’re pleased to report our clinical progress to date with the first microRNA candidate for cancer. MRX34 is a promising, first-in-class therapeutic candidate with potential as a single agent and in combination with targeted and immune therapies. With the safety profile and recommended dose established, we look forward to advancing the development of MRX34 into Phase 2 later in 2016."

The presentation may be accessed from the Events & Presentations section of the Company’s website.