On December 6, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; Nasdaq: MOR) reported its data from the ongoing single-arm phase 2 clinical trial known as L-MIND in an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2018 in San Diego, USA (Press release, MorphoSys, DEC 6, 2018, View Source [SID1234531937]). L-MIND is designed to investigate the antibody MOR208 in combination with lenalidomide in patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). MOR208 is an investigational humanized Fc-enhanced monoclonal antibody directed against CD19 and is currently in clinical development in blood cancer indications.

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The L-MIND study enrolled patients with r/r DLBCL, who are ineligible for HDC and ASCT, after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy, such as rituximab. The updated interim data reported today (cut-off date June 5, 2018) included all 81 patients enrolled in the L-MIND trial, with a median observation time of 12 months. Efficacy results in this update are based on assessment by the investigators for all 81 patients. Patients enrolled had a median age of 72 years and had received a median of two prior treatment lines.

The data showed a response in 47 out of 81 patients (overall response rate, or ORR, 58%), with complete responses (CR) in 27 (33%) and partial responses (PR) in 20 (25%) patients. The median progression-free survival (mPFS) was 16.2 months (95% confidence interval (CI) 6.3 months – not reached). Responses were durable with the median duration of response (DoR) not reached (95% CI: NR – NR) and 70% of responding patients were without progression at 12 months (12-month DoR rate: 70%, Kaplan-Meier estimate). A significant proportion of patients (37/81; 46%) were still on study treatment, with 19 having been treated for over 12 months. Median overall survival (OS) was not reached (95% CI: 18.6 months – NR); the 12-month OS rate was 73% (95% CI: 63% – 85%).

Efficacy parameters, such as response rates and median PFS showed comparable results in most patient subgroups of interest, including low/low-intermediate versus intermediate-high/high IPI score, rituximab refractory versus not refractory and primary refractory versus not refractory, amongst others.

No unexpected toxicities were observed for the treatment combination and no infusion-related reactions (IRRs) were reported for MOR208. The most frequent treatment-emergent adverse events (TEAEs) with a toxicity grading of 3 or higher were neutropenia in 35 (43%), thrombocytopenia in 14 (17%), and anemia in 7 (9%) patients each. Treatment-related serious adverse events (SAEs) occurred in 16 (19.8%) patients, the majority of which were infections or neutropenic fever. 41 (50.6%) patients required dose reduction with lenalidomide, 58 patients (72%) could stay on a daily lenalidomide dose of 20 mg or higher.

The results reported today confirm data from earlier interim analyses reported from this trial in March 2018, when 68 patients had been eligible for investigators’ efficacy assessment at the Dec 12, 2017 cut-off date.

"Patients with relapsed or refractory DLBCL who, after having failed initial therapies, are ineligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT), need more treatment options," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "We are encouraged by our most recent clinical data from the ongoing L-MIND trial. These support our plan to develop MOR208 in combination with lenalidomide, based on our current FDA breakthrough therapy designation, as a potential chemo-free treatment option for this patient population."

Details about the presentation on L-MIND data at ASH (Free ASH Whitepaper) 2018:

Abstract publication number: 227

Session name: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials"

Session date and time: Saturday, December 1, 2018, 4:00pm-5:30pm PST

Presentation time: 5:00pm PST

Room: Marriot Marquis San Diego Marina, Pacific Ballroom 20, San Diego, California.

MorphoSys will hold an investor & analyst event after the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2018 on December 5, 2018, 10:00am EST (3:00pm GMT, 4:00pm CET) in New York. The presentation, a live webcast and a replay of the webcast will be made available at View Source

About DLBCL

Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of malignant lymphoma worldwide and accounts for approximately 30% of all non-Hodgkin lymphomas. Between 30% and 40% of all patients with DLBCL either fail to respond to or show a relapse to initial therapy. Patients who failed frontline therapy and are not eligible to high dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are reported to have a poor outcome and require more therapeutic options.

About CD19 and MOR208

CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.

MOR208 is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be involved in B cell receptor (BCR) signaling.

MorphoSys is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) is investigating the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the U.S. FDA granted Breakthrough Therapy Designation for MOR208 plus lenalidomide in this patient population. The pivotal phase 2/3 B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-

dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. In addition, MOR208 is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.

On December 5, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase III KATHERINE study met its primary endpoint, showing Kadcyla (trastuzumab emtansine) as a single agent significantly reduced the risk of disease recurrence or death (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin (trastuzumab) as an adjuvant (after surgery) treatment in people with HER2-positive early breast cancer (eBC) who have residual disease (pathological invasive residual disease in the breast and/or axillary nodes) present following neoadjuvant (before surgery) treatment (Press release, Hoffmann-La Roche, DEC 5, 2018, View Source [SID1234531903]).[1] At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an 11.3% improvement.[1] Kadcyla improved iDFS irrespective of hormone receptor status, lymph node status and prior HER2-targeted treatment regimen received in the neoadjuvant setting.[1] The safety profile of Kadcyla was consistent with that seen in previous studies, and no unexpected or new safety signals were identified.[1,2,3]

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"The KATHERINE results demonstrate a significant reduction in the risk of recurrence of HER2-positive early breast cancer in people with residual disease after neoadjuvant therapy, and we look forward to submitting these data to health authorities as soon as possible," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We come closer to the goal of helping each person with early breast cancer have the greatest opportunity for cure with every advance in reducing disease recurrence."

The goal in treating eBC is to provide people with the best chance for a cure, which may involve treatment before and after surgery as part of a comprehensive treatment approach.[4;5] While we come closer to this goal with each advance, many people still have a disease recurrence in the long-term.[6] Neoadjuvant treatment is given before surgery with the goal of shrinking tumours and helping to improve surgical outcomes.[5;7;8] Adjuvant treatment is given after surgery and is aimed at eliminating any remaining cancer cells in the body to help reduce the risk of the cancer returning.[5]

These results are being presented in an oral session today at the 2018 San Antonio Breast Cancer Symposium (SABCS) at 11.00 am CST (abstract GS1-10) and featured in the official SABCS press programme at 07.15 am CST. These results will simultaneously be published in the New England Journal of Medicine.

About the KATHERINE study[9]
KATHERINE is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive eBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which, in this study is defined as the time from randomisation free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include disease-free survival and overall survival.

About Kadcyla
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues.[2;3] It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.[10] Kadcyla is the only ADC approved as a single agent in 104 countries including the US and EU for the treatment of people with HER2-positive metastatic breast cancer who have previously received Herceptin and taxane chemotherapy, separately or in combination. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.[11] Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease.

On December 5, 2018 Bristol-Myers Squibb Company (NYSE:BMY) reported that it will announce results for the fourth quarter of 2018 on Thursday, January 24, 2019 (Press release, Bristol-Myers Squibb, DEC 5, 2018, View Source [SID1234531904]). During a conference call at 10:30 a.m. ET on January 24, company executives will review financial information and will address inquiries from investors and analysts.

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Investors and the general public are invited to listen to a live webcast of the call at View Source or by dialing in the U.S. toll free 800-458-4121 or international 786-789-4772, confirmation code: 9368504. Materials related to the call will be available at the same website prior to the conference call. A replay of the call will be available beginning at 1:45 p.m. ET on January 24 through 1:45 p.m. ET on February 7, 2019. The replay will also be available through View Source or by dialing in the U.S. toll free 888-203-1112 or international 719-457-0820, confirmation code: 9368504.

On December 5, 2018 Protagonist Therapeutics, Inc. (NASDAQ:PTGX) reported that Dinesh V. Patel, Ph.D., President and Chief Executive Officer, will provide a corporate overview at the BMO Capital Markets 2018 Prescriptions for Success Healthcare Conference in New York (Press release, Protagonist, DEC 5, 2018, View Source;p=RssLanding&cat=news&id=2379597 [SID1234531922]).

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Presentation details:

Event:

BMO Capital Markets 2018 Prescriptions for Success Healthcare Conference

Date:

Wednesday, Dec. 12, 2018

Time:

9:20 a.m. EST

A live and archived audio webcast of the presentation can be accessed by visiting the Investors page of the Protagonist Therapeutics website at View Source

On December 5, 2018 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that updated data from ongoing Phase I clinical trials of ADCT-402 (loncastuximab tesirine) and ADCT-301 (camidanlumab tesirine) in multiple subtypes of lymphoma during oral and poster presentations at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego (Press release, ADC Therapeutics, DEC 5, 2018, View Source [SID1234596070]).

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"We are encouraged by the safety profiles and strong single-agent anti-tumor activity we continue to observe in the 183-patient first-in-human clinical trial of ADCT-402 and the 113-patient trial of ADCT-301," said Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics. "The updated ADCT-402 data presented at ASH (Free ASH Whitepaper) support its continued evaluation in our ongoing pivotal clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma. For ADCT-301, we now have the dosing data to support further investigation in a planned pivotal Phase II trial in patients with relapsed or refractory Hodgkin lymphoma, which we look forward to initiating in 2019."

ADCT-402 Oral and Poster Presentations at ASH (Free ASH Whitepaper)

Interim Results from the First-in-Human Clinical Trial of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (Abstract 398)

Oral presentation: John Radford, MD, FRCP, Manchester Academic Health Centre, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK

Data were presented from a subpopulation of 139 evaluable patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who had failed or were intolerant to established therapies. The patients had a median age of 63 years and had received a median of three previous therapies. Patients received doses of ADCT-402 ranging from 15 to 200 μg/kg every three weeks. The median number of cycles received was two and the median duration of treatment was 43 days.

Key findings from the oral presentation include:

ADCT-402 has demonstrated manageable toxicity in patients with R/R DLBCL
At doses >120 μg/kg, the overall response rate (ORR) was 43.3% (55/127 patients with DLBCL), comprising 23.6% complete responses and 19.7% partial responses
At doses >120 μg/kg, after a median follow up of 5.5 months, median duration of response (DoR) was not reached in patients achieving a complete response
A pivotal Phase II study is currently enrolling patients with R/R DLBCL to evaluate the efficacy and safety of ADCT-402 at dose 150 μg/kg every three weeks for two cycles followed by dose 75 μg/kg every three weeks (NCT03589469).

Safety and Efficacy of ADCT-402 (Loncastuximab Tesirine), a Novel Antibody Drug Conjugate, in Relapsed/Refractory Follicular Lymphoma and Mantle Cell Lymphoma: Interim Results from the Phase I First-in-Human Study (Abstract 2874)

Poster presentation: Paolo Caimi, MD, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH

Data were presented from a subgroup of 29 patients, including 14 patients with follicular lymphoma (FL) and 15 patients with mantle cell lymphoma (MCL). The median age of the FL patients was 60.5 years and the median age of the MCL patients was 64 years. Patients received infusions every three weeks at doses ranging from 15 to 200 μg/kg. Patients with FL and MCL received a median of three and two cycles of ADCT-402, respectively.

Key findings from the poster presentation include:

ADCT-402 has demonstrated manageable toxicity in patients with R/R FL and R/R MCL
In patients with FL, ORR was 78.6% (11/14) and median DoR was not reached after a median follow-up time of 11.6 months
In patients with MCL, ORR was 46.7% (7/15) and median DoR was not reached after a median follow-up time of 8.7 months
ADCT-301 Oral and Poster Presentations at ASH (Free ASH Whitepaper)

Phase I Study of ADCT-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Classical Hodgkin Lymphoma (Abstract 928)

Oral presentation: Mehdi Hamadani, MD, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI

Data were presented from 67 evaluable, heavily pretreated patients with relapsed/refractory (R/R) classical Hodgkin Lymphoma (HL) who had failed or were intolerant to any established therapy known to provide clinical benefit. The median age of the patients was 38 years and they had received a median of five prior therapies. Patients were treated with doses of ADCT-301 ranging from 5 to 300 μg/kg. They completed a median of three cycles of treatment and median treatment duration was 43 days.

Key findings from the oral presentation include:

ADCT-301 has demonstrated manageable toxicity in patients with R/R HL
The most common Grade 3 or 4 treatment-emergent adverse events occurring in at least 5 percent of patients, regardless of attribution, at the 45 μg/kg dose in 37 patients were: maculopapular rash (18.9 percent),elevated gamma-glutamyltransferase (8.1 percent), elevated alanine aminotransferase (8.1 percent), elevated aspartate aminotransferase (2.7 percent), anemia (8.1 percent), Guillain-Barré syndrome / radiculopathy (8.1 percent) and increased lipase (8.1 percent)
In patients with R/R HL, therapy with ADCT-301 achieved an overall response rate (ORR) of 86.5% and a complete response rate of 43% in the 37 patients in the 45 μg/kg dose group who had received and failed prior brentuximab vedotin and most of whom had failed prior checkpoint inhibitor treatment
These data support further investigation of the 45 μg/kg dose of ADCT-301 in a planned pivotal Phase II study anticipated to commence in 2019
ADCT-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based CD25-Targeting Antibody Drug Conjugate, in a Phase I Study of Relapsed/Refractory Non-Hodgkin Lymphoma Shows Activity in T-Cell Lymphoma (Abstract 1658)

Poster presentation: Graham P. Collins, MB, BS, DPhil, Oxford University Hospitals, NHS Trust, Oxford, UK

Data were presented from 44 patients with R/R non-Hodgkin lymphoma (NHL) with a median age of 65.5 years who had received a median number of four previous systemic therapies (including prior stem cell transplant). Of those, 22 patients were in a T-cell lymphoma subgroup. Patients were treated with doses of ADCT-301 ranging from 3 to 150 μg/kg and received a median number of two cycles. Median treatment duration was 22 days.

Key findings from the poster presentation include:

ADCT-301 demonstrated an acceptable safety profile during dose-escalation
Overall, in patients with R/R NHL, therapy with ADCT-301 achieved an ORR of 31.7% (13/41) at doses >60 μg/kg
In the R/R T-cell lymphoma subgroup, therapy with ADCT-301 achieved an ORR of 53.8% (7/13) in the 60 and 80 μg/kg dose groups
These data support further investigation of ADCT-301 in T-cell lymphoma
About ADCT-402

ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (NCT03589469). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of DLBCL and mantle cell lymphoma.

About ADCT-301

ADCT-301 (camidanlumab tesirine) is an antibody drug conjugate (ADC) composed of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead. The intra-tumor release of its PBD warhead may cause bystander killing of neighboring tumor cells. In addition, the PBD warhead will trigger immunogenic cell death, which in turn will strengthen the immune response against tumor cells. ADCT-301 is being evaluated in ongoing Phase Ia/Ib clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma (NCT02432235), as well as a Phase Ib clinical trial in solid tumors (NCT03621982).