On June 12, 2022 IASO Biotherapeutics ("IASO Bio"), a clinical-stage biopharmaceutical company engaged in discovering, developing, and manufacturing innovative cell therapies and antibody products, and Innovent Biologics, Inc. ("Innovent," HKEX: 01801), reported that the updated data from phase 1/2 study of Equecabtagene Autoleucel (IASO Bio R&D code: CT103A, Innovent R&D code: IBI326), a fully-human anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed and/or refractory multiple myeloma (R/R MM), was presented in the form of an oral presentation at the 27th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Vienna on June 9-12, 2022 (Press release, IASO Biotherapeutics, JUN 12, 2022, View Source [SID1234615912]).

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Presentation Title: Updated Phase 1/2 Data of the Safety and Efficacy of CT103A, Fully-Human BCMA-Directed CAR-T Cells in Relapsed/Refractory Multiple Myeloma
Session Title: Relapsed/refractory myeloma: BCMA-directed therapies
Abstract Code: EHA (Free EHA Whitepaper)-S187
Session date and Time: Sunday, June 12, 2022, at 11:30 AM – 12:45 PM CEST
Place: Vienna, Austria or online
Speaker: Chunrui Li, MD, Ph.D., from Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

The updated data from the Phase 1/2 study with a longer duration of follow-up in more patients has showed durable and deepening efficacy, manageable safety and long-term in vivo persistence, indicating that Equecabtagene Autoleucel has the potential to be a breakthrough therapy for patients with R/R MM.

The updated data is from the 14 clinical sites involved in the Phase 1/2 clinical study of Equecabtagene Autoleucel (ChiCTR1800018137, NCT05066646) in the treatment of patients with R/R MM. As of the data cutoff date of January 21, 2022, 79 patients received recommended phase 2 dose（RP2D）of 1.0×106 CAR-T cells/kg with the median follow-up of nine months (range 1.2, 19.6) and median prior five lines of therapy(range 3,23). Among the 79 patients, 34.2% (27/79) had high-risk cytogenetic abnormalities, 34.2%（27/79）had extramedullary multiple myeloma (EMM), and 15.2%（12/79）had received prior CAR-T therapy.

Equecabtagene Autoleucel demonstrated a favorable and manageable safety profile: Among the 79 patients, 94.9% (75/79) experienced cytokine release syndrome (CRS). The majority experienced 1~2 CRS, and no patient experienced grade 3 CRS. The median time to CRS onset was six days after infusion, and the median duration of CRS was five days. Only two patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), including one patient who experienced grade 1 ICANS and one who experienced grade 2 ICANS. All patients with CRS or ICANS have recovered.

Equecabtagene Autoleucel showed favorable and durable efficacy: Among the 79 patients, the overall response rate (ORR) was 94.9% (75/79), with 89.9 (71/79) of those patients achieving very good partial response (VGPR) or deeper responses, and the complete response/stringent complete response (CR/sCR) rate was 68.4% (54/79). Equecabtagene Autoleucel also demonstrated favorable efficacy in 10 patients with EMM, achieving an ORR of 100% (10/10) and a CR/sCR rate of 90.0% (9/10). In all 79 patients, 92.4% (73/79) achieved minimal residual disease (MRD) negativity, all CR/sCR subjects achieved MRD negativity, and the median duration of MRD negativity was not reached.

Equecabtagene Autoleucel demonstrated favorable efficacy in patients who had received prior CAR-T therapy: Among the 12 patients who previously received CAR-T therapy, the ORR was 75.0% (9/12), with 41.7% (5/12) of those patients achieving CR/sCR.

Equecabtagene Autoleucel demonstrated robust expansion and prolonged persistence: The expansion of Equecabtagene Autoleucel in peripheral blood reached the peak at a median of 12 days, with a median Cmax of 92,000 copies/ug DNA. Equecabtagene Autoleucel was still detectable in 62.3% (38/61) and 53.3% (8/15) of the subjects who completed 6-months and 12-month follow-ups after infusion. Soluble BCMA in peripheral blood of patients rapidly declined after Equecabtagene Autoleucel infusion and persistently remained below the detectable limit.

Equecabtagene Autoleucel has low immunogenicity: 16.5% (13/79) of the subjects tested anti-drug antibody (ADA)-positive after Equecabtagene Autoleucel infusion. Among them，1.3% (1/79) tested ADA-positive before Equecabtagene Autoleucel infusion, and 2.5% (2/79) tested ADA-positive within three months.

"Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. In our previous studies, Equecabtagene Autoleucel has shown excellent efficacy and manageable safety profiles. Its CAR structure contains fully human single-chain fragment variables (scFvs) to bypass potential anti-CAR immunogenicity of the host while retaining antitumor activity. At the 27th EHA (Free EHA Whitepaper) conference, we updated the data on the efficacy and safety of Equecabtagene Autoleucel in R/R MM patients with longer median follow-up extended to 9.0 months, the CR/sCR deepened to 68.4%, compared with the CR/sCR of 58.2% with a median follow-up of 7.0 months, which were released at 63rd ASH (Free ASH Whitepaper) conference in 2021. The updated data showed long-lasting safety and deepening efficacy of Equecabtagene Autoleucel. We are glad that Equecabtagene Autoleucel also shows favorable efficacy on patients who have relapsed after receiving prior CAR-T therapy. This has meaningful clinical value and is worthy of further exploration in the clinic to potentially bring forth new hope to patients with R/R MM." Prof. Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.

About Multiple Myeloma (MM)
Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For multiple myeloma patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there’s currently no cure. As a result, there is a significant unmet need for patients with relapsed/refractory multiple myeloma. In the United States, MM accounts for nearly 2% of new cancer cases and more than 2% of all cancer-related deaths. According to Frost & Sullivan, the number of new MM cases in the United States rose from 30,300 in 2016 to 32,300 in 2020 and is expected to increase to 37,800 by 2025. Additionally, the total number of patients diagnosed with MM increased from 132,200 in 2016 to 144,900 in 2020 and is expected to rise to 162,300 by 2025. In China, the number of new MM cases rose from 18,900 in 2016 to 21,100 in 2020 and is expected to increase to 24,500 by 2025. The total number of patients diagnosed with MM in China increased from 69,800 in 2016 to 113,800 in 2020 and is expected to rise to 182,200 by 2025.

About Equecabtagene Autoleucel
Equecabtagene Autoleucel is an innovative therapy co-developed by Innovent and IASO Bio, with a fully-human anti- BCMA CAR-T cell therapy which uses lentivirus as a gene vector to transfect autologous T cells. The CAR contains a fully-human scFv, CD8a hinge and transmembrane, and 4-1BB-mediated co-stimulation and CD3ζ activation domains. Based on rigorous screening and comprehensive in vivo and in vitro evaluation, Equecabtagene Autoleucel is proven to have potent and rapid anti-myeloma activity and outstanding safety, efficacy, and persistence results.

Equecabtagene Autoleucel was granted "Breakthrough Therapy Designation (BTD)" by the NMPA kn February 2021 and was granted "Orphan Drug Designation (ODD)"by the Office of Orphan Products Development (OOPD) of the U.S. Food and Drug Administration (FDA) in February 2022. The NMPA has accepted the New Drug Application for Equecabtagene Autoleucel for the Treatment of Relapsed and/or Refractory Multiple Myeloma in June 2022.

In addition to multiple myeloma, the NMPA has accepted the investigational new drug (IND) application of Equecabtagene Autoleucel for a new expanded indication of Neuromyelitis Optica Spectrum Disorder (NMOSD).

On June 12, 2022 Novartis reported long-term results from the ELIANA pivotal clinical trial of Kymriah (tisagenlecleucel), the first-ever approved CAR-T cell therapy, in children and young adult patients with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (ALL), with a maximum survival follow-up of 5.9 years (Press release, Novartis, JUN 12, 2022, View Source [SID1234615909]). For the 79 patients treated with Kymriah in this study, the five-year overall survival (OS) rate was 55% (95% CI, 43-66), while the median event-free survival (EFS) for patients in remission within three months of infusion (n=65) was 43.8 months. These findings demonstrate the curative potential of Kymriah, the only CAR-T cell therapy available for these patients who previously had limited treatment options. These data were presented as an oral presentation during the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress (Abstract #S112)1.

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"These data mark a moment of profound hope for children, young adults and their families with relapsed or refractory B-cell ALL, as relapse after five years is rare," said Stephan Grupp, MD, PhD, Section Chief of the Cellular Therapy and Transplant Section, and Inaugural Director of the Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy at Children’s Hospital of Philadelphia (CHOP). "Since the approval of Kymriah nearly five years ago, we have been able to offer a truly game-changing option to patients who previously faced a five-year survival rate of less than 10 percent."

This long-term follow up of ELIANA demonstrated the potential for Kymriah to transform cancer treatment in pediatric and young adult patients with r/r B-cell ALL, significantly improving outcomes with durable responses and a consistent safety profile in this patient population1:

Eighty-two percent of patients experienced remission (either complete remission [CR] or CR with incomplete hematologic recovery within three months after infusion) (95% CI, 72-90)
For patients in remission, the five-year relapse-free survival (RFS) rate was 44% (95% CI, 31-56) and the median RFS was 43 months
No new or unexpected adverse events were reported during long-term follow-up
"At Novartis, we strive for cures. With nearly six-year follow-up data in these pediatric and young adults treated for B-cell ALL, we have our strongest evidence yet that one-time treatment with Kymriah has curative potential," said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development. "These results strengthen our confidence in CAR-T cell therapies as a truly transformative and paradigm-shifting advance in cancer care, as well as our commitment to continue developing this technology with next-generation platforms."

Additional updates on the Novartis CAR-T program presented at the 2022 EHA (Free EHA Whitepaper) Congress include new data from more patients and longer follow-up from the first-in-human dose-escalation trials with YTB323 in adults with r/r diffuse large B-cell lymphoma and PHE885 in adults with r/r multiple myeloma, the first Novartis CAR-T cell therapies developed using the Novartis T-Charge platform2,3,4. Visit View Source to learn more about these data and our ongoing commitment to reimagining cancer care with CAR-T cell therapies.

About Kymriah
Kymriah is the first-ever FDA-approved CAR-T cell therapy. It is a one-time treatment designed to empower patients’ immune systems to fight their cancer. Kymriah is currently approved for the treatment of r/r pediatric and young adult (up to and including 25 years of age) acute lymphoblastic leukemia (ALL), r/r adult diffuse large B-cell lymphoma (DLBCL) and r/r adult follicular lymphoma1.

About the ELIANA Trial
ELIANA was the first pediatric global CAR-T cell therapy registration trial, examining patients in 25 centers in 11 countries across the US, Canada, Australia, Japan and the EU, including: Austria, Belgium, France, Germany, Italy, Norway and Spain. The trial was an open-label, multicenter, single-arm, global Phase II trial investigating the efficacy and safety of Kymriah in pediatric and young adult patients in r/r B-cell ALL who were primary refractory, chemorefractory, relapsed after, or were not eligible for allogeneic stem cell transplantation (SCT). The primary endpoint was overall remission rate (ORR), defined as best overall response of CR or CR with incomplete blood count recovery (CRi) within 3 months and maintained for ≥28 day. The secondary endpoints include CR/CRi with undetectable minimal residual disease (MRD), duration of remission, event-free survival, overall survival, cellular kinetics and safety5.

About T-Charge
T-Charge is a next-generation CAR-T platform, innovated at the Novartis Institutes for BioMedical Research (NIBR), that will serve as the foundation for various new investigational CAR-T cell therapies in the Novartis pipeline. By implementing the T-Charge platform, we aim to revolutionize CAR-T cell therapy with new products that have the potential to offer patients a higher likelihood of better and more durable responses, improved long-term outcomes and a reduced risk of severe adverse events. The T-Charge platform preserves T cell stemness (T cell ability to self-renew and mature), an important T cell characteristic closely tied to its therapeutic potential, which results in a product containing greater proliferative potential and fewer exhausted T cells. With T-Charge, CAR-T cell expansion occurs primarily within the patient’s body (in-vivo), eliminating the need for an extended culture time outside of the body (ex-vivo). The T-Charge platform, which implements important process efficiencies, will be rapid, compared with traditional CAR-T, and reliable, through simplified processes and streamlined quality control. Multiple CAR-T therapies, including YTB323 and PHE885, are being developed using the Novartis T-Charge platform.

About Novartis commitment to Oncology Cell Therapy
As part of the unique Novartis strategy to pursue four cancer treatment platforms – radioligand therapy, targeted therapy, immunotherapy and cell and gene therapy – we strive for cures through cell therapies in order to enable more patients to live cancer-free. We will continue to pioneer the science and invest in our manufacturing and supply chain process to further advance transformative innovation.

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, is the foundation of the Novartis commitment to CAR-T cell therapy.

We have made strong progress in broadening our delivery of Kymriah, which is currently available for use in at least one indication in 30 countries and at more than 370 certified treatment centers, with clinical and real-world experience from administration to more than 6,900 patients. We continue to pioneer in cell therapy, leveraging our vast experience to develop next-generation CAR-T cell therapies. These therapies will utilize our new T-Charge platform being evaluated to expand across hematological malignancies and bring hope for a cure to patients with other cancer types.

On June 11, 2022 Daiichi Sankyo reported that Positive results from the global pivotal QuANTUM-First phase 3 trial of Daiichi Sankyo’s (TSE:5468) quizartinib combined with standard induction and consolidation chemotherapy and then continued as a single agent demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in adult patients aged 18-75 with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML) compared to standard chemotherapy alone (Press release, Daiichi Sankyo, JUN 11, 2022, View Source [SID1234615910]). The data were featured as part of the press program and presented during the Presidential Symposium (#S100) at the European Hematology Association (EHA) (Free EHA Whitepaper) (#EHA2022) Congress.

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AML is one of the most common leukemias in adults with an estimated five-year survival rate of approximately 30.5%.1,2 Of all newly diagnosed cases of AML, 25% carry the FLT3-ITD gene mutation, which is associated with particularly unfavorable prognosis including increased risk of relapse and shorter overall survival.3

Quizartinib combined with standard induction and consolidation chemotherapy and then continued as a single agent demonstrated a 22.4% reduction in the risk of death compared to standard chemotherapy alone (HR = 0.776 [95% CI: 0.615-0.979; 2-sided p=.0324]) in patients with newly diagnosed FLT3-ITD positive AML. After a median follow-up of 39.2 months, median OS was more than double at 31.9 months for patients receiving quizartinib (95% CI: 21.0-NE) compared to 15.1 months for patients receiving chemotherapy (95% CI: 13.2-26.2).

The safety of quizartinib combined with intensive chemotherapy and as continuation monotherapy in QuANTUM-First was generally manageable, with no new safety signals observed. Rates of grade 3 or higher treatment emergent adverse events (TEAEs) were similar for both study groups and the most common grade 3 or higher TEAEs occurring in ≥ 10% of patients were febrile neutropenia (43.4% quizartinib; 41.0% placebo), neutropenia (18% quizartinib; 8.6% placebo), hypokalemia (18.9% quizartinib; 16.4% placebo) and pneumonia (11.7% quizartinib; 12.7% placebo). Rates of TEAEs associated with fatal outcomes were 11.3% for quizartinib versus 9.7% for chemotherapy alone and were mainly due to infections.

QTcF > 500 ms occurred in 2.3% of patients receiving quizartinib and 0.8% of patients discontinued quizartinib due to QT prolongation. Ventricular arrhythmia events with quizartinib were uncommon. Two (0.8%) patients experienced cardiac arrest with recorded ventricular fibrillation on ECG (one with fatal outcome) both in the setting of severe hypokalemia.

"The QuANTUM-First results show that adding quizartinib to standard chemotherapy significantly improved overall survival in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia," said Harry P. Erba, MD, PhD, Instructor, Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute. "There is great interest in the increased use of targeted therapies to improve outcomes for patients with AML, particularly those with the FLT3-ITD subtype, which is one of the most common, aggressive and difficult-to-treat."

"We are proud that another one of our medicines has demonstrated a significant survival advantage, as our goal is to leverage innovative science to change the way cancer is treated," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Adding targeted treatment with quizartinib, a potent and selective FLT3 inhibitor, to standard chemotherapy resulted in a doubling of median overall survival in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia compared to standard chemotherapy alone. Based on these positive QuANTUM-First results, we have initiated global regulatory filings in order to bring quizartinib to patients as quickly as possible."

The OS improvement with quizartinib was also supported by a sensitivity analysis censoring for the effect of allogenic hematopoietic stem cell transplant (HSCT) (HR = 0.752; [95% CI: 0.562-1.008]).

Additional secondary and exploratory analyses provide further understanding and some supporting evidence for improved OS in patients receiving quizartinib combined with chemotherapy in the trial.

The primary event-free survival (EFS) analysis (with induction treatment failure (ITF) defined as not achieving complete remission (CR) by day 42 of the last induction cycle), did not show a statistically significant difference between the two study arms; two pre-specified sensitivity analyses on EFS (the first one defining ITF as not achieving CR by the end of induction; the second one defining ITF as having not achieved composite complete remission (CRc) by the end of induction) showed HR = 0.818 [95% CI: 0.669, 0.999] and HR = 0.729 [95% CI: 0.592-0.897], respectively.

The CRc rate was numerically higher for patients receiving quizartinib compared to chemotherapy alone (71.6% versus 64.9%), and rates of CR were similar for the two study arms (54.9% and 55.4%). The median duration of CR was 38.6 months for quizartinib (95% CI: 21.9-NE) and 12.4 months for chemotherapy (95% CI: 8.8-22.7).

The median relapse-free survival (RFS) for patients who achieved CR was 39.3 months for quizartinib and 13.6 months for placebo, representing a 38.7% relative risk reduction of relapse or death (HR = 0.613 [95% CI: 0.444-0.845]).

*A hierarchical testing procedure was used to test the primary endpoint OS, followed by EFS, CR and CRc. Formal statistical testing was stopped after EFS as its result was not statistically significant.
Data cut-off: August 13, 2021
Abbreviations: HR = Hazard ratio; NE = not estimable; OS = overall survival

About QuANTUM-First

QuANTUM-First is a randomized, double-blind, placebo-controlled global phase 3 study evaluating quizartinib in combination with standard induction and consolidation chemotherapy and then as continued single agent therapy in adult patients (aged 18-75) with newly diagnosed FLT3-ITD positive AML. Patients were randomized 1:1 into two treatment groups to receive quizartinib or placebo combined with anthracycline- and cytarabine-based regimens. Eligible patients, including those who underwent allogeneic HSCT, continued with single agent quizartinib or placebo for up to 36 cycles.

The primary study endpoint was OS. Secondary endpoints include EFS, post-induction rates of CR and CRc, and the percentage of patients who achieve CR or CRc with FLT3-ITD minimal residual disease negativity. Safety and pharmacokinetics, along with exploratory efficacy and biomarker endpoints, also were evaluated. QuANTUM-First enrolled 539 patients at 193 study sites across Asia, Europe, North America, Oceania and South America. For more information, visit ClinicalTrials.gov.

About Acute Myeloid Leukemia (AML)

More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths.4 AML is one of the most common types of leukemia in adults, representing about one-third of all cases, and the average age of diagnosis is 68 years old.1 The five-year survival rate for AML is 30.5%, the lowest by far among the major leukemia subtypes, and is 9.4% for patients aged 65 and older.5,6,7 The conventional treatment for newly diagnosed AML is intensive induction and consolidation chemotherapy with HSCT for eligible patients.8 The introduction of new targeted therapies in recent years has added to the standard of care and improved outcomes for some patients with molecularly defined AML subtypes.9

About FLT3-ITD

FLT3 (FMS-like tyrosine kinase 3) is a tyrosine kinase receptor protein normally expressed by hematopoietic stem cells that plays an important role in cell development, promoting cell survival, growth and differentiation through various signaling pathways.3 Mutations of the FLT3 gene, which occur in approximately 30% of AML patients, can drive oncogenic signaling.3 FLT3-ITD (internal tandem duplication) is the most common type of FLT3 mutation in AML, occurring in about 25% of all newly diagnosed patients, and is associated with increased risk of relapse and shorter overall survival.3

About Quizartinib

Quizartinib is an oral, highly potent and selective type II FLT3 inhibitor currently in clinical development for the treatment of FLT3-ITD positive AML.3 In addition to QuANTUM-First, the quizartinib development program includes a phase 1/2 trial in pediatric and young adult patients with relapsed/refractory FLT3-ITD AML in Europe and North America. Several phase 1/2 combination studies with quizartinib are also underway at The University of Texas MD Anderson Cancer Center as part of a strategic research collaboration focused on accelerating development of Daiichi Sankyo pipeline therapies for AML.

Quizartinib has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive, in combination with standard cytarabine and anthracycline induction and cytarabine consolidation. Orphan Drug Designation has been granted to quizartinib for the treatment of AML in Europe, Japan and the U.S.

Quizartinib is currently approved for use in Japan under the brand name VANFLYTA for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, as detected by an approved test. Quizartinib is an investigational medicine in all countries outside of Japan.

On June 11, 2022 Genmab A/S (Nasdaq: GMAB) reported that primary results from the large B-cell lymphoma (LBCL) expansion cohort in the EPCORE NHL-1 phase 2 clinical trial evaluating subcutaneous epcoritamab (DuoBody-CD3xCD20), an investigational bispecific antibody (Press release, Genmab, JUN 11, 2022, View Source [SID1234615908]). In the study, treatment with epcoritamab demonstrated deep and durable responses with an overall response rate (ORR) of 63 percent and a complete response rate (CR) of 39 percent in patients who had previously received at least two prior lines of systemic anti-lymphoma therapy. Additionally, patients naïve to treatment with chimeric antigen receptor (CAR) T-cell therapy achieved 69 percent ORR and 42 percent CR and patients previously treated with CAR T achieved a 54 percent ORR and 34 percent CR. Data were presented in a late-breaking oral presentation as a part of the Presidential Symposium at the 27th Annual Meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA2022) in Vienna, Austria (Abstract #LB2364).

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"Large B-cell lymphoma is a fast-growing, difficult to treat type of aggressive non-Hodgkin’s lymphoma. Some treatment approaches like chemotherapy and immunotherapy have been in place for decades and newer treatments like CAR T-cell therapies involve multiple steps before a patient can begin treatment, so there is still a need for additional treatment options," said Professor Catherine Thieblemont, Head of the Hemato-Oncology Department at Hôpital Saint-Louis, Paris, France. "The data presented today suggest that epcoritamab has the potential to provide patients living with relapsed/refractory LBCL an accessible, effective treatment with a safety profile that may fulfill an unmet need."

The study cohort, which included 157 relapsed/refractory LBCL patients, previously treated with a median of three lines of prior therapy, demonstrated an overall response rate (ORR) of 63 percent and a complete response rate (CR) of 39 percent. Baseline characteristics included 61 percent of patients who were refractory to primary treatment, 20 percent who had prior autologous stem cell transplantation (ASCT), and 39 percent who were treated with CAR T-cell therapy (75 percent of those refractory to CAR T). Patients enrolled in the study who were naïve to CAR T therapy achieved a 69 percent ORR and a 42 percent CR and patients who received prior CAR T-cell treatment achieved a 54 percent ORR and a 34 percent CR. After a median follow up of 10.7 months, the median duration of response (mDOR) was estimated to be 12 months, while the mDOR among patients achieving a CR was not reached, with 89 percent still in CR at nine months. Topline results from this study were previously announced in April 2022.

"These latest data are promising because they suggest that treatment with epcoritamab may benefit patients with this fast-growing, aggressive and difficult to treat type of non-Hodgkin’s lymphoma who are in need of new therapeutic advances," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We are encouraged by the potential of epcoritamab and look forward to continuing to advance our robust clinical development program with our partner, AbbVie."

The safety profile of epcoritamab was manageable and consistent with previous findings. The majority of treatment-emergent AEs (TEAEs) occurred during the first 12 weeks of treatment and resolved. The most common TEAEs of any grade (greater than or equal to 15 percent) included cytokine release syndrome (CRS) (49.7 percent), pyrexia (23.6 percent), fatigue (22.9 percent), neutropenia (21.7 percent), diarrhea (20.4 percent), injection site reaction (19.7%), nausea (19.7%), and anemia (17.8%). The most common Grade 3 or 4 treatment-emergent adverse events (greater than or equal to 5 percent) included neutropenia (14.6 percent), anemia (10.2 percent), neutrophil count decrease (6.4 percent), and thrombocytopenia (5.7 percent). The observed Grade 3 CRS was low (2.5 percent). No Grade 4/5 CRS was observed.

Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration. The companies remain committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy for a variety of hematologic malignancies, including an ongoing phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory DLBCL (NCT: 04628494).

About Large B-cell Lymphoma (LBCL)
LBCL is a fast-growing type of non-Hodgkin’s lymphoma (NHL) – a cancer that develops in the lymphatic system – that affects B-cell lymphocytes, a type of white blood cell. There are an estimated 150,000 new LBCL cases each year globally. LBCL includes DLBCL, which is the most common type of NHL worldwide and accounts for approximately 31 percent of all NHL cases.1,2,3,4

About the EPCORE NHL-1 Trial
EPCORE NHL-1 an open-label, multi-center safety and preliminary efficacy trial of epcoritamab including a phase 1 first-in-human, dose escalation part; a phase 2 expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-NHL, including LBCL and DLBCL. The dose escalation findings, which determined the recommended phase 2 dose, were published in The Lancet in 2021. In the phase 2 expansion part, additional patients are treated with epcoritamab to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who had limited therapeutic options.

The primary endpoint of the phase 2 expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were evaluated as secondary efficacy endpoints.

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 towards 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.5 Epcoritamab was developed with selective, silencing mutations that may limit systemic, non-specific activity. CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.6,7 Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

On June 11, 2022 Oxford Drug Design reported that it will be attending the 28th tRNA Conference, 12-16 June 2022 in Columbus, Ohio, USA (Press release, Oxford Drug Design, JUN 11, 2022, View Source [SID1234615907]). On 13 June at 4:45pm EST Paul will be participating in a Panel Discussion on "Emerging Opportunities in tRNA Therapeutics", which will showcase the emerging opportunities for translational science and entrepreneurism in tRNA-related therapeutics and biotechnology across multiple therapeutic areas and treatment modalities. This is an exciting area with untapped therapeutic potential in which Oxford Drug Design is taking a leading position.

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