On December 10, 2023 Dizal reported the full analysis of the multinational pivotal study of golidocitinib for r/r PTCL (JACKPOT8 PART B) in an oral presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (2023 ASH (Free ASH Whitepaper), San Diego) (Press release, Dizal Pharma, DEC 10, 2023, View Source [SID1234638388]). The results were simultaneously published in the prestigious peer-reviewed journal The Lancet Oncology (Impact Factor: 54.4). This follows the publication of the Phase I clinical data of golidocitinib for the treatment of r/r PTCL (JACKPOT8 PART A) in Annals of Oncology (Impact Factor: 51.8) three months ago.

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Golidocitinib is currently the first and only Janus kinase 1 (JAK1) selective inhibitor being evaluated for the treatment of r/r PTCL. A total of 104 patients with r/r PTCL were enrolled in the JACKPOT8 PART B study to evaluate the efficacy and safety of golidocitinib as a monotherapy. At the cut-off date of August 31, 2023, per independent review committee (IRC) assessment, 70% of patients achieved target lesion size reduction, yielding an overall response rate (ORR) of 44.3%, and a complete response rate (CRR) of 23.9%. Tumor responses were observed across various PTCL subtypes. The responses were durable, with the median duration of response (mDoR) of 20.7 months. The median progression-free survival (mPFS) was 5.6 months, and the median overall survival (mOS) was 19.4 months and still ongoing. As a potent JAK1 inhibitor with > 200 to 400-fold selectivity over other JAK family members, golidocitinib demonstrated a favorable safety profile. The most common treatment-related adverse events (TRAEs) were reversible and clinically manageable. These findings highlight the potential of golidocitinib to offer robust and durable clinical benefits for patients with r/r PTCL.

"PTCL is a highly heterogeneous and aggressive non-Hodgkin lymphoma (NHL) with the characteristics of various subtypes, high recurrence rate and poor prognosis. Patients with r/r PTCL have limited treatment options and a poor prognosis with a low survival rate. The efficacy of current treatment modalities varies among different r/r PTCL subtypes." said Jun Zhu, MD, PhD at the Department of Lymphoma, Peking University Cancer Hospital and Institute, the correspondence author of the paper, "The JAK/STAT signaling pathway plays a pivotal role in the pathogenesis and progression of various hematologic malignancies, including T-cell malignancies. Consequently, targeting the JAK/STAT pathway emerges as an innovative and highly promising treatment option for PTCL. Golidocitinib is an oral, potent, JAK1 only inhibitor with superior selectivity and favorable pharmacokinetic properties, offers robust and sustained inhibition of the JAK/STAT pathway while maintaining optimal clinical safety."

"In the JACKPOT8 PART B study, more than 100 patients with r/r PTCL were enrolled. The efficacy analysis of 88 patients revealed an ORR of 44.3%, with 23.9% achieving complete response. Notably, a consistently high ORR was observed across various PTCL subtypes. The median DoR for golidocitinib was 20.7 months, mPFS reached 5.6 months, and mOS was 19.4 months." said Yuqing Song, MD, PhD at the Department of Lympho-Oncology of Peking University Cancer Hospital, the lead author of the paper, "Golidocitinib demonstrates superior ORR and survival results as compared to the current available treatment options and offers hope for improving the poor prognosis of patients with r/r PTCL. These findings present innovative therapeutic possibilities and paves the way towards better patient outcomes."

"It is gratifying to see the increasing recognition of golidocitinib’s potential as a new therapy for patients with PTCL." said Xiaolin Zhang, Ph.D., Chairman and CEO of Dizal, "Patients with r/r PTCL have long been facing limited treatment options and a poor prognosis. Golidocitinib stands as a major achievement resulting from Dizal’s dedicated translational science efforts. Its superior efficacy and safety, as demonstrated through compelling global pivotal trials, bring hope for these underserved patients."

These findings, highlighting the superior efficacy and safety of golidocitinib, have been widely acknowledged at prestigious conferences including ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper), ICML, and ASH (Free ASH Whitepaper), with six oral presentations over four consecutive years. In September 2023, the NDA for golidocitinib was accepted by the CDE with Priority Review status for the treatment of r/r PTCL. Dizal continues to expand the scope of clinical research on golidocitinib and explore its application in a broader patient population. At 2023 ASH (Free ASH Whitepaper), Dizal will also announce positive results of golidocitinib as maintenance therapy for patients with PTCL after first-line systemic therapy in a phase 2 study (JACKPOT26).

About golidocitinib (DZD4205)

Golidocitinib is currently the first and only Janus kinase 1 (JAK1) selective inhibitor being evaluated for the treatment of r/r PTCLs. At the data cut-off date of August 31, 2023, Golidocitinib has demonstrated robust and durable anti-tumor activity, with an ORR of 44.3%. More than 50% of the patients with tumor remission achieved a complete response with a CRR of 23.9%. Per IRC assessment, mDoR reached 20.7 months. Golidocitinib was granted Fast Track Designation by the U.S. FDA for the treatment of r/r PTCL in February 2022. In September 2023, the CDE accepted the NDA and granted the Priority Review status for the treatment of r/r PTCL. The Phase I clinical data of golidocitinib for the treatment of r/r PTCL (JACKPOT8 PART A) was published in Annals of Oncology (Impact Factor: 51.8), and global pivotal trials data of golidocitinib for the treatment of r/r PTCL (JACKPOT PART B) was published in The Lancet Oncology (Impact Factor: 54.4).

On December 10, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported new and updated data for odronextamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (Press release, Regeneron, DEC 10, 2023, View Source [SID1234638373]). The data from the pivotal Phase 2 trial (ELM-2) and Phase 1 trial (ELM-1) were shared in several presentations – including two orals – at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition from December 9 to 12 in San Diego, CA. Odronextamab is an investigational CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.

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"Diffuse large B-cell lymphoma has a high risk of relapse, which is why it is so critical to demonstrate continued disease control over the long term. The totality of the odronextamab data at ASH (Free ASH Whitepaper) reinforces its potential as a promising treatment option for patients with this aggressive blood cancer," said Sabarish Ram Ayyappan, M.D., medical director of hematologic malignancies, City of Hope Atlanta, and a trial investigator. "The primary analysis from the pivotal trial of odronextamab demonstrated impressive response rates, including in certain high-risk subgroups. Furthermore, these responses were durable and consistent with those seen in a Phase 1 trial in patients who had previously progressed on CAR-T therapy, a population with a very poor prognosis."

As presented in an oral session, the primary Phase 2 analysis was performed by independent central review (ICR) among 127 DLBCL patients treated with odronextamab when all had the opportunity for ≥36 weeks of follow-up. Results were as follows:

52% objective response rate (ORR), with 31% achieving a complete response (CR).
Responses were observed across high-risk subgroups, including those with International Prognosis Index (IPI) high-risk scores of 3 to 5, high-grade lymphoma that is double-hit and triple-hit, and transformed DLBCL.
Median duration of response (DoR) was 10 months (95% confidence interval [CI]: 5 to 18 months), with a 30-month median duration of follow-up for efficacy evaluable patients (95% CI: 20 to 33 months). The median duration of CR was 18 months (95% CI: 10 months to not estimable [NE]).
The most common adverse events (AE) in ≥30% patients were cytokine release syndrome (CRS; 55%), pyrexia (43%), anemia (39%) and neutropenia (31%).
In 60 patients that received the recommended step-up regimen, 53% experienced CRS. All cases were resolved with supportive measures, with a median duration of 2 days (range: 1 to 7 days). Among these patients, 40% (n=24) had Grade 1 CRS, 12% (n=7) had Grade 2 CRS, and 2% (n=1) had Grade 3 CRS.
No events of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.
An additional analysis from the Phase 1 trial demonstrated encouraging and durable antitumor activity with odronextamab in heavily pretreated patients who had progressed after CAR-T therapy. Median duration of exposure was 11 weeks (range: <1 to 122 weeks) among 46 treated patients. Results among 44 efficacy-evaluable patients, including 73% who were CAR-T refractory, as assessed by ICR showed:

48% ORR, with 30% achieving a CR. Notably, 8 patients converted from a partial response to a CR over the study period.
Both median DoR and median duration of CR were not reached (95% CI: 2 to NE) with a 5-month median duration of follow-up (95% CI: 3 to 9 months).
The most common AEs in ≥30% of patients were CRS (52%), anemia, pyrexia and fatigue (each 34%). All CRS events were resolved, with a median time to resolution of 2 days (range: 1 to 8 days). Among these patients, 27% (n=12) had Grade 1 CRS and 25% (n=11) had Grade 2 CRS.
In a separate oral presentation on an exploratory analysis from the Phase 2 trial, data showed a positive association between minimal residual disease (MRD) status, as measured by circulating tumor DNA (ctDNA), and progression-free survival (PFS). Among 70 R/R DLBCL and 65 R/R follicular lymphoma (FL) patients assessed, nearly all were MRD-positive at baseline. Notably, those who were MRD-negative at time of the first response assessment (Cycle 4, Day 15) had significantly longer PFS than those who remained MRD-positive (DLBCL Hazard Ratio [HR]: 0.27, 95% CI: 0.12 to 0.61; FL HR: 0.26, 95% CI: 0.1 to 0.66).

"Our research is among the first to analyze circulating tumor DNA in a pivotal trial in relapsed/refractory stages of diffuse large B-cell lymphoma and follicular lymphoma," said Jon E. Arnason, M.D., hematologist and oncologist, Beth Israel Deaconess Medical Center, and a trial investigator. "These findings strengthen the body of evidence supporting the importance of minimal residual disease status as a monitoring tool in the course of managing patients with lymphoma. As the data for circulating tumor DNA continues to grow, these insights may help inform future response-directed treatment paradigms."

Odronextamab is currently under regulatory review for the treatment of R/R DLBCL and R/R FL by the U.S. Food and Drug Administration (FDA), with a target action date of March 31, 2024, as well as by the European Medicines Agency (EMA). In the U.S., odronextamab has been granted Fast Track Designation for DLBCL and FL by the FDA. In the European Union, odronextamab has been granted Orphan Drug Designation in DLBCL and FL by the EMA.

The potential use of odronextamab in R/R DLBCL and R/R FL is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority.

Investor Webcast Information
Regeneron will host a conference call and simultaneous webcast to share updates on the company’s hematology portfolio on Thursday, December 14 at 8:30 AM ET. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

About the Odronextamab Clinical Program
ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20-positive B-cell malignancies previously treated with CD20-directed antibody therapy. The trial includes an expansion cohort evaluating DLBCL patients who had progressed on CAR-T therapy.

ELM-2 is an ongoing, open-label, multicenter pivotal Phase 2 trial investigating odronextamab in 375 patients across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-cell non-Hodgkin lymphoma (B-NHL). The primary endpoint of ELM-2 is ORR according to the Lugano Classification, and secondary endpoints include CR, PFS, overall survival, DoR, disease control rate, safety and quality of life.

Regeneron has initiated a broad Phase 3 development program to investigate odronextamab in earlier lines of therapy and other B-NHLs, representing one of the largest clinical programs in lymphoma.

About Diffuse Large B-cell Lymphoma (DLBCL)
DLBCL is one of the most common subtypes of B-NHL. In the U.S., it is estimated that approximately 31,000 people will be diagnosed with DLBCL in 2023. Globally, there are an estimated 163,000 DLBCL cases each year. DLBCL is an aggressive cancer with up to 50% of patients with advanced stage disease progressing after first-line treatment (e.g., relapsing or becoming refractory to treatment). For patients with relapsed/refractory DLBCL, treatment options are limited, and prognosis is poor.

On December 10, 2023 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the clinical data of lisaftoclax (APG-2575), one of the company’s key drug candidates, combined with various novel therapies in patients with relapsed/refractory (R/R) multiple myeloma (MM) or immunoglobulin light-chain (amyloid light-chain [AL]) amyloidosis, in a Poster Presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in San Diego, CA, the United States (Press release, Ascentage Pharma, DEC 10, 2023, View Source;ascentage-pharma-releases-the-first-dataset-of-bcl-2-inhibitor-lisaftoclax-in-patients-with-rr-mm-demonstrating-encouraging-orr-and-vgpr-302010980.html [SID1234638389]). This is the first data readout of lisaftoclax for the treatment of patients with R/R MM.

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The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma’s key drug candidates (lisaftoclax and olverembatinib) have been selected for presentations at this year’s ASH (Free ASH Whitepaper) Annual Meeting, including two Oral Presentations.

These data signalled the favorable therapeutic potential and tolerability of lisaftoclax combination regimens in patients with hematologic malignancies such as R/R MM. Results showed an overall response rate (ORR) of 66.7% and a very good partial response (VGPR) rate of 28.6% in patients with R/R MM who received lisaftoclax combined with pomalidomide and dexamethasone; and an ORR of 100% and a VGPR rate of 50% in patients with R/R MM who received lisaftoclax combined with daratumumab, lenalidomide, and dexamethasone. Lisaftoclax was well tolerated at doses up to the maximum of 1,200 mg.

Prof. Sikander Ailawadhi, MD, from Mayo Clinic and the principal investigator of this study, commented, "It was the first time to issue efficacy of lisaftoclax in patients with R/R MM, with an outstanding overall response rate. Lisaftoclax was well tolerated even when the combination dose was escalated up to 1200 mg. At the same time, the efficacy of lisaftoclax for patients with AL amyloidosis is also showing up."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "At this year’s ASH (Free ASH Whitepaper) Annual Meeting, we presented data of lisaftoclax combinations in patients with malignant plasmocyte diseases such as R/R MM that demonstrated promising ORR, VGPR; and favorable tolerability at doses up to 1,200 mg. These results reaffirmed the global best-in-class potential and unique therapeutic utility of lisaftoclax. Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring safe and effective therapies to patients in need."

Highlights of the study presented at ASH (Free ASH Whitepaper) 2023:

First Report on the Effects of Lisaftoclax (APG-2575) in Combination with Novel Therapeutic Regimens in Patients with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light-Chain (Amyloid Light-Chain [AL]) Amyloidosis

Format: Poster Presentation
Abstract: #2016
Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster I
Time: December 9, 2023, Saturday, 5:30 PM – 7:30 PM (Pacific Time) / December 10, 2023, Sunday, 9:30 AM – 11:30 AM (Beijing Time)
Highlights
Background: Lisaftoclax is an investigational, novel, potent, selective Bcl-2 inhibitor under clinical development for treatment of patients with hematologic malignancies or solid tumors and has shown clinical antitumor benefits. In a previous study on chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and other hematologic malignancies, lisaftoclax was shown to require only a short dose ramp-up to mitigate tumor lysis syndrome (TLS) and was associated with a low incidence of adverse events (AEs). This multicenter study was designed to evaluate the safety and efficacy of lisaftoclax combination regimens in patients with R/R MM or R/R AL amyloidosis.

Methods:

This study has three treatment arms that included Arm A: lisaftoclax combined with pomalidomide and dexamethasone in patients with R/R MM; Arm B: lisaftoclax combined with daratumumab, lenalidomide, and dexamethasone in patients with R/R MM; and Arm C: lisaftoclax combined with pomalidomide and dexamethasone in patients with R/R AL amyloidosis.
Lisaftoclax was administered orally once daily (QD) at 5 dose levels (400 mg, 600 mg, 800 mg, 1,000 mg, and 1,200 mg) without ramp-up in 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use. Dexamethasone 40 mg (20 mg for patients aged >75 years) was administered on Days 1, 8, 15, and 22 of 28-day cycles.
Patients: As of July 3, 2023, a total of 30 patients were enrolled. Among them, 22, 3, and 5 patients were enrolled into Arms A, B, and C, respectively. 66.7% of patients were male, and the median (range) age was 70.5 (24-88) years. All patients were previously exposed to multiple lines of treatment. 18 (60%) patients were triple-class-exposed, 7 (35%) had received pomalidomide and 3 (10%) harbored the t(11;14) chromosomal abnormality.

Efficacy results:

In Arm A, 21 patients with R/R MM were efficacy evaluable, including 6 (28.6%) who have reached VGPRs and 8 (38.1%) who have reached partial responses (PRs), resulting in an ORR (PR + VGPR) of 66.7%.
In Arm B, 1 patient with R/R MM achieved PR and another achieved VGPR, resulting in an ORR of 100%.
In Arm C, 3 patients with R/R amyloidosis achieved a hematologic VGPR, resulting in an ORR of 60%; 1 patient achieved improvement in organ functions.
Conclusions: Lisaftoclax combination regimens were well tolerated and demonstrated potent antitumor activity (especially VGPRs and PRs) in patients with R/R MM and R/R AL amyloidosis.

* Lisaftoclax (APG-2575) is an investigational drug that has not been approved in any country and region.

On December 10, 2023 Sanofi reported that the Phase 3 trial investigating Sarclisa (isatuximab) in combination with carfilzomib, lenalidomide and dexamethasone (KRd) showed a statistically significant improvement in the rate of minimal residual disease (MRD) negativity, compared with KRd alone, after autologous stem cell transplant (ASCT) consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (MM) (Press release, Sanofi, DEC 10, 2023, View Source [SID1234638374]). These results from the IsKia trial conducted by the European Myeloma Network (EMN) were presented during the oral plenary session (#4) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Francesca Gay, Associate Professor at the University Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Torino and Department of Molecular Biotechnology and Health Sciences – member of the Young EMN board of directors.

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MRD negativity is defined as the absence of myeloma cells in the bone marrow after treatment, as measured by diagnostic techniques that must have a sensitivity of at least 1 in 100,000 cells. In this trial, MRD negativity was detected with a sensitivity of 10-5 (no cancer cells detected within 100,000 bone marrow cells) and 10-6 (no cancer cells detected within 1,000,000 bone marrow cells).

In an intent-to-treat (ITT) analysis, the primary endpoint of rate of MRD negativity using next generation sequencing with a sensitivity of 10-5 after consolidation for patients receiving Sarclisa combination therapy (n=151) was 77% versus 67% for those who received KRd alone (n=151) (odds ratio [OR] 1.67; p=0.049). The respective rates of MRD negativity at sensitivity of 10-6 were 67% versus 48% (OR 1.93; p=0.006). The MRD negativity benefit, both at 10-5 and 10-6 sensitivities, was retained in all subgroups analyzed with similar benefit in both standard-risk and high-risk patients.

There was a statistically significant difference in MRD negativity rates after induction with Sarclisa in combination with KRd versus KRd (10-5: 45% versus 26%, p<0.001; 10-6: 27% versus 14%, p=0.004).

The safety and tolerability of Sarclisa observed in this trial were consistent with the observed safety profile of Sarclisa in other clinical trials, with no new safety signals observed. Rates of grade 3 or higher hematologic adverse events (AEs) were 40% versus 30% and rates of non-hematologic AEs were 41% versus 37% for the Sarclisa combination versus KRd, respectively. Discontinuation rates for AEs were similar in both study arms (7% and 5%, respectively). There were three treatment-related deaths in the Sarclisa combination arm and one in the KRd arm.

Peter C. Adamson
Global Development Head, Oncology, Sanofi

"The statistically significant rates of MRD negativity observed with Sarclisa combination therapy further support our belief in Sarclisa as a potential best-in-class therapy. Effective front-line treatment is critical for newly diagnosed patients, because achieving undetectable levels of disease early in the treatment journey may lead to better long-term outcomes. We look forward to our continued collaboration with the EMN to explore the potential of this novel combination regimen for those with transplant-eligible, newly diagnosed multiple myeloma."

The use of Sarclisa in combination with KRd in this patient population is investigational and has not been evaluated by any regulatory authority.

About the trial

The randomized, open-label Phase 3 IsKia trial enrolled 302 patients with newly diagnosed, transplant-eligible MM across eight countries and 42 sites in Europe. Patients were randomized into two arms. Patients in both arms received induction with four 28-day cycles of KRd followed by cyclophosphamide and stem cell collections, chemotherapy with Melphalan 200 mg/m2 followed by ASCT (Mel200-ASCT), four 28-day cycles of KRd post ASCT consolidation and 12 cycles of KRd light consolidation. Sarclisa was added to KRd in one trial arm only. During the trial, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for the first four weeks of cycle one, then every other week for the rest of the induction and full consolidation periods, then every four weeks during light consolidation period.

The primary endpoint was the rate of MRD negativity by next-generation sequencing (10-5) after consolidation in the ITT population. MRD was tested in all patients who achieved at least a very good partial response. Key secondary endpoints were the rate of next-generation sequencing MRD negativity (10-5) after induction and progression free survival. MRD rates were evaluated in an ITT analysis.

High-risk patient cytogenetics per the International Myeloma Working Group (IMWG) criteria were defined as the presence of t(4;14), t(14;16), or del(17p). High-risk cytogenetic abnormality (HRCA) was defined as the presence of one of the following abnormalities: del(17p13.1), t(4;14) (p16.3;q32.3), t(14;16) (q32.3;q23), gain(1q21), or amp(1q21). Two or more HRCAs was defined as the presence of at least two high-risk cytogenetic abnormalities.

About Sarclisa

Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activities. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.

Based on the Phase 3 ICARIA-MM study, Sarclisa is approved in >50 countries, including the U.S. and EU, in combination with pomalidomide and dexamethasone for the treatment of certain patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the Phase 3 IKEMA study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the U.S. for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the U.S., the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA).

The IsKia trial marks the second positive Phase 3 trial of Sarclisa in transplant-eligible newly diagnosed multiple myeloma, and fifth positive Phase 3 readout for Sarclisa overall, demonstrating its best-in-class potential.

Sarclisa continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.

For more information on Sarclisa clinical trials, please visit www.clinicaltrials.gov.

About multiple myeloma

MM is the second most common hematologic malignancy.1 Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

On December 10, 2023 Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-dose epigenetic editing therapeutics, reported data demonstrating the potential of its multiplex epigenetic editing platform to enhance functional allogeneic chimeric antigen receptor (CAR) T cells at the American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Meeting in San Diego (Press release, Chroma Medicine, DEC 10, 2023, View Source [SID1234638390]).

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Allogeneic CAR T cell products offer advantages over autologous CAR T cells and have the potential to broaden access to cancer immunotherapy; however, their clinical effect remains limited by lack of durable response and challenges related to immunogenicity and graft-versus-host disease. Incorporating additional edits may help produce cells resistant to rejection—potentially improving allogeneic T cell persistence—but using editing technologies that rely on double- or single-stranded DNA breaks can result in unintended genomic changes. Chroma’s epigenetic editing technology has the potential to provide durable modulation of gene expression without cutting or nicking the DNA, making it well-suited for simultaneous targeting of multiple genes to enhance generation of persistent allogeneic CAR T cells.

"The data presented at ASH (Free ASH Whitepaper) illustrate the tremendous potential of epigenetic editing to accelerate allogeneic CAR T approaches by enhancing functional allogeneic cells to avoid common genotoxic challenges observed in nuclease-based gene editing and base editing," said Vic Myer, Ph.D., Chroma’s President and CSO. "We believe harnessing nature’s innate mechanism for gene regulation unlocks vast opportunity to efficiently, effectively, and simultaneously silence many target genes, and the data presented underscore the strength of this approach in ex vivo cell therapies."

The poster presentation shows Chroma’s epigenetic editor in primary T cells induces durable silencing of T cell receptor and MHC class I and MHC class II expression, maintained through restimulation. The data also demonstrate that multiplex epigenetic editing of CAR T cells does not interfere with cytotoxic anti-tumor function, further highlighting the potential to create CAR T cell therapies with greater accessibility, durability, and efficacy for patients.

Details for Chroma’s poster presentation at the 2023 ASH (Free ASH Whitepaper) Annual Meeting are as follows:

Title: Durable Multiplex Epigenetic Editing for Generation of Allogeneic CAR T Without Chromosomal Rearrangements
Presenter: Jamie Schafer, Ph.D., Associate Director, Ex Vivo Program Sciences, Chroma Medicine
Session: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Session Date and Time: Sunday, December 10, 2023, 6:00 – 8:00p PT

The poster presentation is available on Chroma’s website.