On December 11, 2022 AbbVie (NYSE: ABBV) reported data from multiple clinical trials evaluating epcoritamab (DuoBody-CD3xCD20), an investigational subcutaneous bispecific antibody, alone or in combination for the treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL), previously untreated FL, R/R diffuse large B-cell lymphoma (DLBCL), as well as Richter’s syndrome at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, AbbVie, DEC 11, 2022, View Source [SID1234625009]).

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Notably, initial results of investigational epcoritamab in patients with R/R FL and previously untreated FL are featured during session 623 on Sunday, December 11 starting at 4:30 p.m. CST. The results are part of the EPCORE NHL-2 study, a Phase 1b/2, open-label trial to assess the safety and preliminary efficacy of epcoritamab in combination with other agents in patients with B-cell non-Hodgkin’s lymphoma, including FL. Approximately 2.7 per 100,000 people in the U.S. are newly diagnosed with FL every year and the median age of patients at diagnoses with FL is 63.1,2,3 FL is typically a slow-growing or indolent form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.4 Although FL is a slow-growing lymphoma, it is considered incurable with conventional therapy.5,6

"These data at this year’s ASH (Free ASH Whitepaper) meeting are promising as they support continued investigation of epcoritamab for patients in need of new treatment options for follicular lymphoma and other B-cell lymphomas," said Mohamed Zaki, M.D., Ph.D., vice president and head, global oncology development, AbbVie. "Along with Genmab, we look forward to continuing to build on our promise of exploring a potential core therapy for patients with B-cell malignancies in a variety of treatment settings."

Additional results from the EPCORE NHL-2 study as well as the EPCORE CLL-1 study were presented for investigational epcoritamab in R/R DLBCL and Richter’s syndrome respectively. The EPCORE CLL-1 study is an open-label, multi-center, safety and efficacy trial of epcoritamab in R/R chronic lymphocytic leukemia (CLL) and Richter’s syndrome. The trial consists of two parts, a dose escalation Phase (Phase Ib) and an expansion Phase (Phase II).7

Abstract #609: Subcutaneous Epcoritamab with Rituximab + Lenalidomide in Patients with Relapsed or Refractory Follicular Lymphoma: Phase 1/2 Trial Update

Oral Presentation: Sunday, December 11, 2022 at 5:00 p.m. CST

In the R/R FL arm of the EPCORE NHL-2 trial, 95 percent (63/66) of efficacy-evaluable patients treated with subcutaneous epcoritamab in combination with rituximab and lenalidomide achieved an overall response rate (ORR) and 80 percent (53/66) achieved complete metabolic response (CMR). The majority of patients achieved a response at first tumor response assessment and most continued to respond through the latest assessment at the time of data collection.

A manageable cytokine release syndrome (CRS) occurrence was observed with only low-grade events, mainly following the first full dose, all of which resolved. The most common treatment-emergent adverse events (TEAEs) of any grade were neutropenia (47%), CRS (43%), injection-site reactions (32%), fatigue (31%), constipation (25%), COVID-19 (25%), pyrexia (25%) and infusion-related reaction (21%).

Abstract #611: Subcutaneous Epcoritamab in Combination with Rituximab + Lenalidomide for First-Line Treatment of Follicular Lymphoma: Initial Results from Phase 1/2 Trial

Oral Presentation: Sunday, December 11, 2022 at 5:30 p.m. CST

In the previously untreated FL patient arm of the EPCORE NHL-2 trial, 94 percent (34/36) of efficacy-evaluable patients who received subcutaneous epcoritamab in combination with rituximab and lenalidomide achieved an ORR, including 86 percent (31/36) achieving CMR as their best overall response. In the trial, the investigational combination therapy showed a manageable CRS occurrence with only low-grade events, all of which resolved.

The most common TEAEs of any grade were CRS (54%), neutropenia (47%), pyrexia (44%), fatigue (37%), injection-site reaction (37%), headache (34%), COVID-19 (33%), diarrhea (32%), constipation (29%), rash (27%), increased alanine aminotransferase (ALT) (22%), and vomiting (22%).

Abstract #443: Subcutaneous Epcoritamab + R-Dhax/C in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Eligible for Autologous Stem Cell Transplant: Updated Phase 1/2 Results

Oral Presentation: Sunday, December 11, 2022 at 10:30 a.m. CST

Results from the EPCORE NHL-2 arm evaluating 27 patients with R/R DLBCL who were eligible for autologous stem cell transplant, showed an 85 percent (23/27) ORR and 67 percent (18/27) CMR following treatment with the combination of subcutaneous epcoritamab plus standard rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin (R-DHAX/C) salvage therapy.

The most common TEAEs of any grade were thrombocytopenia (69%), anemia (51%), neutropenia (44%), CRS (41%), nausea (31%), fatigue (28%), constipation (24%), diarrhea (24%), headache (24%), pyrexia (24%) and increased aspartate aminotransferase (AST) (21%). All CRS events were low-grade and resolved.

Abstract #348: Subcutaneous Epcoritamab in Patients with Richter’s Syndrome: Early Results from Phase 1b/2 Trial (EPCORE CLL-1)

Oral Presentation: Saturday, December 10, 2022 at 5:15 p.m. CST

Preliminary results from the EPCORE CLL-1 trial showed that treatment with subcutaneous epcoritamab monotherapy had promising antitumor activity in 10 patients with Richter’s syndrome, with a 60 percent ORR and a 50 percent CMR rate. Most responses were observed by the first assessment at week six. In the trial, patients experienced only low-grade CRS events, mostly associated with the first full dose, all of which resolved.

The most common TEAEs of any grade were CRS (90%), anemia (50%), neutropenia (50%), injection-site reaction (40%), thrombocytopenia (40%), hypophosphatemia (30%), Hypokalemia (30%), hyperglycemia (30%), COVID-19 (30%), diarrhea (30%), fatigue (30%), and nausea (30%).

About Diffuse Large B-Cell Lymphoma (DLBCL)
DLBCL is a fast-growing type of NHL that affects B-cell lymphocytes, a type of white blood cell.8 It is the most common type of NHL worldwide and accounts for approximately 30 percent of all NHL cases.8 DLBCL can arise in lymph nodes, as well as in organs outside of the lymphatic system.8 The disease occurs more commonly in the elderly and is slightly more prevalent in men.8

About Richter’s Syndrome
Richter’s syndrome, also known as Richter’s transformation, is defined as the transformation of CLL into an aggressive lymphoma, most commonly DLBCL.9,10 Richter’s syndrome occurs in approximately 2 percent to 10 percent of CLL patients during the course of their disease.9

About the EPCORE NHL-2 Trial
EPCORE NHL-2 is a Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard-of-care agents in subjects with B-cell non-Hodgkin’s lymphoma. The trial consists of two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion).11

The primary objective of Part 1 is safety, and it includes Arm 1–5. Part 2 includes all 8 arms (Arm 1–8) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Patients in Arm 1–5 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities will be assessed in Part 1 and for a selected number of patients in Arm 8 during a 28-day period (safety-run Phase). The arms are conducted in parallel.11

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T-cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells and induces T-cell mediated killing of CD20+ cells.12 CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including DLBCL, FL, mantle cell lymphoma and CLL.13,14

AbbVie recently announced that the Biologics License Application (BLA) for epcoritamab for the treatment of adult patients with R/R large B-cell lymphoma after two or more lines of systemic therapy was accepted for priority review by the U.S. Food and Drug Administration. Additionally, the European Medicines Agency has validated a Marketing Authorization Application for epcoritamab for the treatment of adult patients with R/R DLBCL after two or more lines of systemic therapy.

Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan with AbbVie responsible for further global commercialization. The companies are committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes an ongoing Phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) and a Phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R FL (NCT: 05409066).

On December 10, 2022 On December 10, 2022, Sangamo Therapeutics, Inc., or Company, reported updated preliminary proof-of-concept clinical data from the Phase 1/2 PRECIZN-1 study of BIVV003, a zinc finger nuclease gene-edited autologous cell therapy product candidate for the treatment of sickle cell disease, or SCD, at the 64th American Society for Hematology Annual Meeting and Exposition, or ASH (Free ASH Whitepaper) (Press release, Sangamo Therapeutics, DEC 10, 2022, View Source [SID1234625142]). Also on December 11, 2022, the Company presented at ASH (Free ASH Whitepaper) updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A in development with Pfizer Inc. Summaries of the data presented are below.

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Summary of Updated Preliminary Safety, Tolerability and Efficacy Results from the Phase 1/2 PRECIZN-1 Study of BIVV003 Presented at ASH (Free ASH Whitepaper)

•PRECIZN-1 is an ongoing, first-in-human, open label, single arm, multi-site study evaluating the safety, tolerability and efficacy of BIVV003 in patients with severe SCD (n=8; aged 18-40 years).

•Eligible patients underwent mobilization and apheresis with plerixafor. Autologous hematopoietic stem and progenitor cells, or HSPCs, were transfected ex vivo with zinc finger nuclease messenger ribonucleic acid to manufacture BIVV003. A single intravenous infusion was administered at least 72 hours after pre-conditioning with busulfan.

•Patients were monitored for stem cell engraftment and hematopoietic recovery, adverse events, clinical and laboratory hemolysis markers, total hemoglobin, or Hb, and fetal hemoglobin, or HbF, percentage of F cells and SCD-related events post‑BIVV003 infusion.

•Six patients achieved successful target yields of HSPCs. Five of the six patients achieving successful target yields of HSPCs had been infused with BIVV003 as of the September 30, 2022 cutoff date. Baseline characteristics of these five patients are in Table 1 below. The first four patients dosed received BIVV003 produced using the initial manufacturing process and are referred to in Table 1 below as Group 1. Group 1 patients have been followed for up to 30 months post-infusion. The patient referred to in Table 1 below as Group 2 received BIVV003 manufactured using improved methods that have been shown in internal experiments to increase the number of long-term progenitor cells in the final product. As of the cutoff date, the first patient treated in Group 2, or Patient 5, had been followed for 5 months. A second patient in Group 2 was dosed after the cutoff date.

•Four of five patients in aggregate across both Groups 1 and 2 improved clinically since BIVV003 infusion through the September 30, 2022, cutoff date.

In Group 1:

•The effects of BIVV003 infusion on total Hb and HbF levels were maintained up to 30 months.

•Three of the four patients had stable engraftment of zinc finger nuclease-modified HSPCs, resulting in sustained elevated HbF levels greater than 30% and an absence of severe vaso-occlusive crisis, or VOCs, post-BIVV003 administration.
In Group 2:

•Patient 5 received BIVV003 manufactured using improved methods that have been shown in internal experiments to increase the number of long-term progenitor cells in the final product.

•The HbF level of 45% and total Hb of 12.4 g/dL at week 26 post-infusion for Patient 5 in the latest sample collected post data cutoff were greater than the levels observed in Group 1 at week 26.

•As of the September 30, 2022 cutoff date, BIVV003 was generally well tolerated, and most adverse events reported in the screening, mobilization, apheresis and conditioning periods were SCD-related events. The investigator reported two serious adverse events of sickle cell anemia with a VOC as related to plerixafor, and one serious adverse event of nausea as related to busulfan. Nearly half of the adverse events reported after infusion of BIVV003 were related to busulfan. The investigator reported two serious adverse events of sickle cell anemia with a VOC nine months and 16 months after infusion in the one patient in Group 1 who had low HbF levels (11-14%). No other SCD-related serious adverse events were reported after infusion. No adverse events related to BIVV003 were reported by the investigator or sponsor. See Figure 2 below for VOCs reported before and after infusion of BIVV003.

Number of severe vaso-occlusive crises (VOCs) reported in the 24 months before signing the study informed consent form (ICF) and in the post-BIVV003 infusion period.
Red lines represent severe VOCs; 2 severe VOCs occurring in the same month appear as one red line
Group 1 includes the first four patients dosed, who received BIVV003 produced using the initial manufacturing process.
Group 2 includes patient 5 who received BIVV003 manufactured using improved methods that have been shown in internal experiments to increase the number of long-term progenitor cells in the final product.
Summary of Updated Follow-up Data from the Phase 1/2 Alta Study of Giroctocogene Fitelparvovec Presented at ASH (Free ASH Whitepaper)
•Alta is a Phase 1/2 single-dose multicenter dose-ranging study to assess the safety and tolerability of giroctocogene fitelparvovec in adults with severe hemophilia A.
•Patients were monitored for adverse events, change in circulating Factor VIII, or FVIII, activity, change from baseline in use of FVIII replacement therapy, change in frequency and severity of bleeding episodes, measurement of FVIII inhibitor levels and vector shedding in bodily fluids.
•Maintenance of FVIII activity in the mild range (>5%) or greater improves outcomes for patients with severe hemophilia A.
•Eleven male patients participated in the study overall, with five patients in the 3e13-vg/kg highest dose cohort. See Table 1 below for baseline patient demographics. As of the September 6, 2022 cutoff date, all patients had been followed for 153 to 263 weeks and all participants have completed at least 35 months of follow-up.
•As of the September 6, 2022 cutoff date, six of the eleven patients had experienced treatment-related adverse events, including four of the five patients in the highest dose cohort. The most commonly reported treatment-related adverse events included elevated liver enzymes and infusion-related reactions: increased alanine aminotransferase, or ALT (5/11 (45.5%) overall; 3/5 (60.0%) in the highest dose cohort), increased aspartate aminotransferase, or AST (3/11 (27.3%) overall; 2/5 (40.0%) in the highest dose cohort), pyrexia (3/11 (27.3%) overall; 3/5 (60.0%) in the highest dose cohort), and tachycardia (2/11 (18.2%) overall; 2/5 (40.0%) in the highest dose cohort).
•Treatment-related serious adverse events were reported in one patient in the highest dose cohort who experienced grade 3 hypotension and fever with onset approximately six hours after giroctocogene fitelparvovec infusion; the events fully resolved with treatment and did not delay post-infusion discharge the next day. See Table 2 below for more details on treatment-related adverse events.
•As of the September 6, 2022 cutoff date, no confirmed FVIII inhibitor development occurred, and no thrombotic events, neoplastic events, abnormal alfa-fetoprotein and/or liver masses were reported.

•All five patients in the highest dose cohort demonstrated FVIII activity as shown in Table 3 below through week 156. Mean FVIII activity at week 156 was 25.5% of normal as measured by chromogenic clotting assay at the central laboratory. In this highest dose cohort, the annualized bleeding rate, meaning the number of all bleeding episodes starting three weeks after infusion divided by the observation period in years, was zero for the first year post-infusion and the mean overall annual bleeding rate throughout the total duration of follow-up was 1.2 as of the September 6, 2022 cutoff date.
•In this highest dose cohort, two patients experienced bleeding events necessitating treatment with exogenous FVIII: one patient experienced 17 bleeding events (8 traumatic, 5 spontaneous, 4 unknown), and one patient experienced one bleeding event in a target joint, circumstances unknown. No participants in this highest dose cohort have resumed prophylaxis as of the cutoff date.
•Additional follow-up is required to assess durability of therapeutic effect and other long-term effects of giroctocogene fitelparvovec, such as impact on overall patient liver health.

On December 10, 2022 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported topline data from its phase 2 REDIRECT study investigating AFM13 monotherapy in patients with advanced-stage r/r PTCL (Press release, Affimed, DEC 10, 2022, View Source [SID1234625068]).

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Primary efficacy measures include ORR of 32.4% and a complete response (CR) rate of 10.2%. Key secondary and exploratory outcome measures include safety, durability of response, progression free survival and overall survival. The safety profile of AFM13 was well managed and consistent with previously reported data of prior and ongoing clinical studies with AFM13. Median DoR was 2.3 months, median PFS was 3.5 months and median OS was 13.8 months.

"These are remarkable data for AFM13 as a single agent and they confirm that the activation of innate immunity can lead to robust clinical activity," said Dr. Adi Hoess, Chief Executive Officer at Affimed. "Our parallel study investigating AFM13 in combination with allogeneic NK cells shows that this combination can materially improve clinical outcomes for patients with CD30-postive lymphomas. We will therefore be focusing further development of AFM13 in PTCL on the combination with NK cells to improve the durability of response and build on the already meaningful activity with the goal of obtaining regulatory approval to give this difficult to treat patient population another therapeutic option."

"The activity of AFM13 in heavily pretreated patients with peripheral T cell lymphoma is very encouraging with an objective response rate of 32% and a PFS of 3.5 months," said Dr. Won Seog Kim, Professor of Hematology-Oncology at Samsung Medical Center in Seoul and a principal investigator for the study. "The data demonstrate that the innate immune system can successfully attack lymphomas and thus AFM13 provides a new mechanism of action that could expand our options in treating this difficult disease."

REDIRECT is a registration-directed phase 2 open-label, multicenter, global study investigating the efficacy and safety of AFM13 monotherapy in patients with CD30-positive r/r PTCL. The primary outcome measure was the objective response rate (ORR) following treatment with AFM13 as measured by an independent review committee (IRC) by FDG-PET. Secondary and exploratory outcome measures included DoR, PFS, OS, the safety of AFM13 as well as pharmacokinetics and immunogenicity of AFM13. In the trial, 108 patients received treatment with AFM13 as weekly intravenous infusions of 200 mg for the duration of the trial participation. Disease assessment was conducted at screenings every 8 weeks for the first 2 assessments and every 12 weeks thereafter.

Peripheral T cell lymphomas are highly aggressive and one of the most difficult to treat forms of lymphoma with very poor prognosis for patients. Based on the compelling data seen in Hodgkin lymphoma for the combination of AFM13 with cord blood-derived NK cells in the AFM13-104 study, the Company believes that the combination with AB-101 has a higher probability to deliver increased anti-tumor activity and a more durable clinical benefit to address the unmet need in this patient population. Accordingly, Affimed does not intend to pursue an accelerated approval for AFM13 monotherapy in PTCL and will focus investment on clinical development in the combination of AFM13 with Artiva’s AB-101 NK cell product.

Investor Event & Webcast Details

Affimed will host an investor event to review AFM13 clinical data and development plans in CD30 expressing malignancies. The investor event will take place in-person and virtually and a webcast of the event will be available in the "Webcasts" section on the "Investors" page of Affimed’s website at View Source To access the event via phone, please dial +1 (929) 205-6099 for U.S. callers, or +44 (203) 481-5240 for international callers, and reference meeting ID 847 4106 6227 approximately 15 minutes prior to the call. To reserve your place in the live event, please contact Alex Fudukidis via e-mail at [email protected].
A replay of the webcast/call will be archived on Affimed’s website for 30 days after the call.

About AFM13

AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma (REDIRECT). Additional details can be found at www.clinicaltrials.gov (NCT04101331).

The study achieved an ORR of 32.4% demonstrating anti-tumor activity with a DOR of 2.3 months and a well-managed safety profile. AFM13 is a tetravalent bispecific innate cell engager designed to act as a bridge between the innate immune cells and the tumor creating the necessary proximity for the innate immune cells to specifically destroy the tumor cells.

On December 10, 2022 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported a data update from the ongoing phase 1/2 study of the Company’s lead innate cell engager (ICE) AFM13 precomplexed with cord blood-derived natural killer (cbNK) cells in patients with CD30-positive relapsed or refractory Hodgkin and Non-Hodgkin lymphomas (Press release, Affimed, DEC 10, 2022, View Source [SID1234625067]). The results are being presented today at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by principal investigator Yago Nieto, M.D., Ph.D., Professor of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. Results from the study continue to demonstrate high objective and complete response rates with a well-tolerated safety profile.

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In 31 patients with Hodgkin lymphoma treated at the RP2D, an ORR of 97% and a CR rate of 77% were observed. In four non-Hodgkin lymphoma patients treated at the RP2D, three objective responses, including one CR in a patient with peripheral T-cell lymphoma, were observed. Across all 35 patients treated at the RP2D, a 94% ORR and a CR rate of 71% were observed.

"It’s impressive that we continue to see these response rates in a patient population that has exhausted all other treatment options. As a physician, when I consider that all patients in this study did not respond to their previous line of treatment, these results are especially meaningful," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed.

Duration of response (DOR) continues to be monitored, and key observations as of the cutoff date include:

63% of patients with at least 6 months follow-up after initial infusion (n=24) remain in CR for at least 6 months
18 of 33 responders at the RP2D remain in response as of the cutoff date, including 17 of 25 patients with a CR
Five patients treated at the RP2D had their response consolidated with a stem cell transplant
The treatment continues to be well tolerated in the larger patient population, with minimal side effects beyond the expected myelosuppression from the preceding lymphodepleting chemotherapy. No instances of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft versus host disease were observed. There were 20 infusion-related reactions in 294 infusions (6.8%) of AFM13 alone and one infusion-related reaction in 99 infusions (1%) of the cord blood-derived NK cells precomplexed with AFM13. No dose-limiting toxicities were encountered.

"These data further confirm that combining our AFM13 innate cell engager with cord blood-derived natural killer cells has the potential to provide a truly transformative treatment for patients with limited therapeutic options," commented Dr. Adi Hoess, Chief Executive Officer at Affimed. "Our focus and commitment together with our new partner Artiva is expected to bring AFM13 in combination with NK cells to the market as quickly as possible for the benefit of patients with CD30-positive lymphomas."

AFM13, a bispecific tetravalent ICE molecule, is designed for high affinity binding, both to CD16A on NK cells and macrophages, and to CD30 on lymphoma cells.

Oral Presentation Details

Title: Innate Cell Engager AFM13 Combined with Preactivated and Expanded Cord Blood-Derived NK Cells for Patients with Double Refractory CD30+ Lymphoma
Session: Cellular Immunotherapies: Early Phase and Investigational Therapies: Lymphoma
Presentation Date & Time: Saturday, December 10, 2022, 1:15 p.m. CST
Location: Ernest N. Morial Convention Center, La Nouvelle Orleans Ballroom AB

Investor Event, Conference Call and Webcast Information

Affimed will host an investor event to review AFM13 clinical data and development plans in CD30-expressing malignancies. The investor event will take place in-person and virtually and a webcast of the event will be available in the "Webcasts" section on the "Investors" page of Affimed’s website at View Source To access the event via phone, please dial +1 (929) 205-6099 for U.S. callers, or +44 (203) 481-5240 for international callers, and reference meeting ID 847 4106 6227 approximately 15 minutes prior to the call. To reserve your place in the live event, please contact Alex Fudukidis via e-mail at [email protected]. A replay of the webcast/call will be archived on Affimed’s website for 30 days after the call.

About the AFM13-104 Phase 1/2 Study

The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored phase 1/2 trial in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive lymphomas. The study is a dose-escalation trial of precomplexed NK cells, followed by an expansion phase recruiting up to 40 patients with r/r CD30 positive lymphomas at the RP2D of 1×108 NK cells/kg. Each treatment cycle consists of lymphodepleting chemotherapy with fludarabine (30 mg/m² per day) and cyclophosphamide (300 mg/m² per day) followed two days later by a single infusion of cytokine-preactivated and expanded cord blood-derived NK cells that are pre-complexed with AFM13. Three weekly infusions of AFM13 (200 mg) monotherapy are subsequently administered and responses are assessed by the investigator on day 28 by FDG-PET.

MD Anderson has an institutional financial conflict of interest with Affimed related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan. Additional information about the study can be found at www.clinicaltrials.gov (NCT04074746). As of the cut-off date, 41 patients with relapsed or refractory CD30-positive Hodgkin and Non-Hodgkin lymphoma were treated in the study, all of whom were evaluable for response. The patients treated in the study have received a median of seven prior lines of therapy. After the first 13 patients treated at the RP2D, the protocol was amended to allow patients to receive up to 4 cycles, whereas previously patients were only eligible for 2 cycles.

About AFM13

AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma (REDIRECT). Additional details can be found at www.clinicaltrials.gov (NCT04101331).

On December 10, 2022 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported final safety and efficacy results from firstMIND, a Phase 1b, open-label, randomized safety study combining tafasitamab or tafasitamab plus lenalidomide with standard R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) (Press release, MorphoSys, DEC 10, 2022, View Source [SID1234625066]). Additional analyses highlighted the prognostic potential of sensitive circulating tumor (ct) DNA minimal residual disease (MRD) assays in patients with DLBCL after first-line therapy. These results are being presented during oral and poster sessions on December 10, 2022, at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in New Orleans, Louisiana.

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Tafasitamab, marketed in the U.S. as Monjuvi and outside the U.S. by Incyte as Minjuvi, is a CD19 targeting immunotherapy. Tafasitamab received an accelerated approval and conditional approval by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively, for patients with certain types of DLBCL that has come back (relapsed) or that did not respond to previous treatment (refractory) and who are not eligible to receive a stem cell transplant.

"The final analysis from firstMIND underscores the therapeutic potential of tafasitamab in combination with lenalidomide added on to standard R-CHOP therapy for patients with newly diagnosed DLBCL," said Greg S. Nowakowski, M.D., Professor of Medicine and Oncology at the Mayo Clinic and lead investigator for the firstMIND trial. "This regimen, which is also being investigated in the Phase 3 frontMIND trial, represents an ongoing effort to address a critical need in patients with high-risk DLBCL, many of whom relapse after current first-line therapy. I am encouraged by the results from firstMIND and eagerly anticipate the Phase 3 data on the combined efficacy of tafasitamab, lenalidomide and R-CHOP in newly diagnosed patients with DLBCL."

The final analysis of firstMIND demonstrated an overall response rate at the end of treatment of 75.8% for patients treated with tafasitamab plus R-CHOP (n=33) and 81.8% for patients treated with tafasitamab, lenalidomide and R-CHOP (n=33). In the tafasitamab, lenalidomide and R-CHOP arm, 24-month progression-free survival (PFS) and overall survival (OS) rates were 76.8% and 93.8%, respectively. PFS and OS rates were 73.6% and 95.2%, respectively, for patients with high-intermediate to high-risk DLBCL (International Prognostic Index [IPI] 3-5) treated with tafasitamab, lenalidomide and R-CHOP (n=22). Improved PFS was observed in MRD-negative patients compared with MRD-positive patients.

The most common hematological treatment emergent adverse events in both patients treated with tafasitamab plus R-CHOP and patients treated with tafasitamab, lenalidomide and R-CHOP were neutropenia (60.6% and 84.8%, respectively), anemia (51.5% and 60.6%), thrombocytopenia (21.2% and 42.4%) and leukopenia (30.3% and 27.3%), respectively. Rates of febrile neutropenia were equal (18.2%) in both arms. Non-hematological adverse events were well balanced between arms and were mostly grades 1 and 2. No unexpected toxicities or new safety signals were identified in the final analysis.

A second poster presentation and an oral presentation both demonstrate the potential of sensitive ctDNA MRD assays to predict PFS outcomes following first-line treatment in patients with DLBCL. In the poster presentation, negative MRD as detected by next generation sequencing detection of ctDNA after treatment with tafasitamab in combination with lenalidomide and R-CHOP in the firstMIND study was associated with a significant improvement in PFS (p=0.008). One of 12 patients who were MRD-negative after treatment had developed disease progression by the time of data cutoff, when all patients had completed 18 months of post-treatment follow-up.

The oral presentation highlighted the prognostic utility of sensitive ctDNA MRD assays in a meta-analysis of five prospective studies of first-line treatment regimens for large B-cell lymphomas. Achievement of MRD negativity after any of the first three cycles of treatment was strongly prognostic for PFS (p=0.0003), and failure to achieve MRD negativity by the end of treatment was associated with the highest risk for progression. Detection of ctDNA MRD at levels below 1 in 10,000 (0.01%) was essential to achieve 99% sensitivity.

"These new data suggest that assays that can better detect minimal residual disease carry important prognostic value and may serve as surrogate markers for clinical benefit in future lymphoma trials," said Dr. Tim Demuth, Chief Research and Development Officer at MorphoSys. "These insights, along with the final results from firstMIND and growing body of data supporting Monjuvi in second-line therapy, give us greater understanding of how to improve outcomes at diagnosis or first relapse. We are eager to learn through frontMIND about the potential of tafasitamab plus lenalidomide to augment a standard of care in first-line therapy for patients newly diagnosed with high-intermediate and high-risk DLBCL."