CD38 inhibitors(Lymphocyte differentiation antigen CD38 inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects), Antibody-dependent cellular phagocytosis (ADCP) effects

Therapeutic Areas

NeoplasmsImmune System DiseasesCardiovascular Diseases+ [6]

Active Indication

Immunoglobulin Light-Chain AmyloidosisMultiple MyelomaResidual Neoplasm+ [16]

Inactive Indication

Extranodal NK-T-Cell LymphomaFollicular LymphomaMantle cell lymphoma refractory+ [6]

Originator Organization

Janssen Global Services LLC

Active Organization

Johnson & Johnson (China) Investment Ltd.Janssen Research & Development LLC

Janssen Pharmaceutica NV

+ [13]

Inactive Organization

Dana-Farber Cancer Institute, Inc.

Celgene Corp.

Drug Highest PhaseApproved

First Approval Date

US (16 Nov 2015),

Multiple Myeloma

RegulationBreakthrough Therapy (US), Fast Track (US), Accelerated Approval (US), Orphan Drug (US), Orphan Drug (EU), Priority Review (CN), Orphan Drug (JP), Paediatric investigation plan (EU), Orphan Drug (GB), Priority Review (JP)

Gene Sequence

Sequence Code 9075449L

Source: *****

Sequence Code 9946743H

Source: *****

311

Clinical Trials associated with Daratumumab

NCT06169215 / RecruitingPhase 2IIT

A Randomized Phase 2 Study of Daratumumab-Selinexor-Velcade-Dexamethasone (Dara-SVD) for High-Risk Newly Diagnosed Multiple Myeloma

This phase II trial compares the combination of selinexor, daratumumab, Velcade (bortezomib), and dexamethasone (Dara-SVD) to the usual treatment of daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVD) in treating patients with high-risk newly diagnosed multiple myeloma. Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may keep cancer cells from growing and may kill them. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Bortezomib blocks several molecular pathways in a cell and may cause cancer cells to die. It is a type of proteasome inhibitor and a type of dipeptidyl boronic acid. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. The drugs daratumumab, lenalidomide, bortezomib, dexamethasone and selinexor are already approved by the FDA for use in myeloma. But selinexor is not used until myeloma comes back (relapses) after initial treatment. Giving selinexor in the initial treatment may be a superior type of treatment for patients with high-risk newly diagnosed multiple myeloma.

Start Date16 Nov 2024

Sponsor / Collaborator

National Cancer Institute

NCT06348147 / Not yet recruitingPhase 2IIT

An Attenuated Schedule Dara-RVd Induction for Patients With Newly Diagnosed Multiple Myeloma Who Are Eligible for Autologous Stem Cell Transplantation

This Phase II hybrid decentralized trial will examine the effect of daratumumab-based quadruplet induction therapy administered at an attenuated schedule in subjects with newly diagnosed multiple myeloma (NDMM) who are eligible for standard-of-care autologous stem cell transplantation (ASCT). Daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-RVd) have recently become a standard induction regimen for patients with NDMM who are eligible for ASCT in the United States. As implemented in clinical trials, Dara-RVd involves twice weekly bortezomib administration, which is inconvenient for patients and may result in increased rates of limiting toxicity, such as peripheral neuropathy. Adoption of alternate schedules involving once-weekly bortezomib is common in real-world practice, however a paucity of prospective data supporting this practice exists.
This study examines the efficacy of an attenuated Dara-RVd schedule involving once-weekly bortezomib dosing.

Start Date01 Aug 2024

Sponsor / Collaborator

UNC Lineberger Comprehensive Cancer Center

NCT06022939 / Not yet recruitingPhase 3IIT

A Phase III, Randomized Study of Daratumumab, Cyclophosphamide, Bortezomib and Dexamethasone (Dara-VCD) Induction Followed by Autologous Stem Cell Transplant or Dara-VCD Consolidation and Daratumumab Maintenance in Patients With Newly Diagnosed AL Amyloidosis

This phase III trial compares the effect of adding a stem cell transplant with melphalan after completing chemotherapy with daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) versus chemotherapy with Dara-VCD alone for treating patients with newly diagnosed amyloid light chain (AL) amyloidosis. Melphalan is a chemotherapy given prior to a stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. The stem cells are then returned to the patients to replace the blood forming cells that were destroyed by the chemotherapy. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs, such as cyclophosphamide and bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to lower the body's immune response to help stop the growth of cancer cells. Giving a stem cell transplant with melphalan after Dara-VCD may kill more cancer cells in patients with newly diagnosed AL amyloidosis.

Start Date01 Jul 2024

Sponsor / Collaborator

SWOG

[+1]

100 Clinical Results associated with Daratumumab

100 Translational Medicine associated with Daratumumab

100 Patents (Medical) associated with Daratumumab

1,458

Literatures (Medical) associated with Daratumumab

01 Mar 2024·American journal of hematology

Efficacy and safety of daratumumab with ixazomib and dexamethasone in lenalidomide‐exposed patients after one prior line of therapy: Final results of the phase 2 study DARIA

Article

Author: Malandrakis, Panagiotis ; Dimopoulos, Meletios A ; Kastritis, Efstathios ; Delimpasi, Sosana ; Manousou, Kyriaki ; Symeonidis, Argiris ; Katodritou, Eirini ; Terpos, Evangelos ; Verrou, Evgenia ; Gavriatopoulou, Maria ; Ntanasis-Stathopoulos, Ioannis ; Golfinopoulos, Stavros ; Hatjiharissi, Evdoxia ; Migkou, Magdalini

Abstract:

The use of lenalidomide in frontline therapy for patients with newly diagnosed multiple myeloma (MM) has increased the number of those who become refractory to lenalidomide at second line. In this context, we assessed the efficacy of daratumumab in combination with ixazomib and dexamethasone (Dara‐Ixa‐dex) in the prospective phase 2 study DARIA. Eligible patients had relapsed/refractory MM (RRMM) after one prior line with a lenalidomide‐based regimen. The primary endpoint was overall response rate (ORR). Secondary endpoints included survival outcomes, safety and changes in biomarkers of bone metabolism. Overall, 50 patients were enrolled (median age 69 years, 56% males). 32 (64%) patients were refractory to lenalidomide, and 17 (34%) had undergone autologous transplant. The ORR was 64% (n = 32); whereas 17 (34%) had a very good partial response or better. The median time to first response was 1.0 month. After a median follow‐up of 23.4 months, the median PFS and OS were 8.1 and 39.2 months, respectively. Furthermore, significant changes in markers of bone metabolism became evident as early as at 6 months on treatment. Regarding safety, 21 (42%) patients had ≥1 grade 3/4 adverse event (AE); the most common was thrombocytopenia (n = 9, 18%). 14 (28%) patients had ≥1 serious AE (SAE), the most common being acute kidney injury and pneumonia (n = 2, each). Four patients died due to infections. In conclusion, second‐line treatment with Dara‐Ixa‐dex in patients with RRMM pre‐treated with a lenalidomide‐based regimen resulted in rapid responses along with a favorable effect on bone metabolism.

01 Feb 2024·American journal of hematology

Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment

Article

Author: Gertz, Morie A

Abstract:

Disease Overview:

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and “atypical smoldering multiple myeloma or MGUS.”

Diagnosis:

Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.

Prognosis:

N‐terminal pro–brain natriuretic peptide (NT‐proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5‐year survivals are 82%, 62%, 34%, and 20%, respectively.

Therapy:

All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first‐line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.

Future Challenges:

Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end‐stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.

Haematologica

Daratumumab and brentuximab vedotin combination therapy in T-cell acute lymphoblastic leukemia refractory to conventional chemotherapy and allogeneic stem cell transplant

Article

Author: Begna, Kebede H ; Gangat, Naseema ; Mangaonkar, Abhishek A ; Janania-Martinez, Michelle ; Abdallah, Nadine H ; Rangan, Aruna ; Herrick, Jennifer L

Not available.

339

News (Medical) associated with Daratumumab

18 Jun 2024

·www.prnewswire.com

Live from EHA 2024 | Ascentage Pharma Releases Updated Data of Lisaftoclax in Patients with R/R MM and AL Amyloidosis Highlighting Marked Improvement in ORR

SUZHOU, China and ROCKVILLE, Md., June 18, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that it has released updated data of the Bcl-2 inhibitor lisaftoclax (APG-2575), one of the company's key drug candidates, combined with novel therapeutic regimens in patients with relapsed/refractory (R/R) multiple myeloma (MM) or immunoglobulin light-chain (AL) amyloidosis, in a poster presentation at the 2024 European Hematology Association Hybrid Congress (EHA 2024), taking place in Madrid, Spain. Building on results from the study released for the first time at the 2023 American Society of Hematology Annual Meeting, the updated data presented at EHA 2024 continued to show impressive efficacy and favorable safety of lisaftoclax-based combinations, particularly the combination with pomalidomide and dexamethasone in R/R MM. Moreover, the study reported an incidence of Grade 3 or higher treatment-related neutropenia of 14.3%, which underscored the regimens' potential in offering patients a safe new treatment option. Prof. Sikander Ailawadhi, MD, from Mayo Clinic and the principal investigator of this study, commented, "This is a study of lisaftoclax combined with novel therapeutic regimens in patients with R/R MM or AL amyloidosis. From the primary analysis, it demonstrated that lisaftoclax + pomalidomide in R/R MM could achieve ≥very good partial response (VGPR) rate of 33.3%, and higher VGPR along with increasing lisaftoclax dosage. Moreover, lisaftoclax based therapy in both R/R MM and amyloidosis is very well tolerated with Grade 3/4 neutropenia of 14.3%. This convincing data could provide an alternative treatment option to patients with MM and amyloidosis." "It is our pleasure to release the updated data of lisaftoclax in patients with R/R MM or AL amyloidosis at this year's EHA Hybrid Congress," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "These data underscore the outstanding safety and efficacy profiles of the combination therapies, once again demonstrating these regimens' global best-in-class potential. We will actively advance this clinical development program to bring patients a safe and effective new treatment option as soon as possible." The EHA Hybrid Congress is the largest gathering of the hematology field in Europe. It showcases the most cutting-edge research and state-of-the-art innovative therapies, attracting over 10,000 clinical experts and researchers from more than 100 countries every year. This year, in addition to the latest data of lisaftoclax, Ascentage Pharma also released those of the third-generation BCR-ABL1 inhibitor olverembatinib (HQP1351) and the EED inhibitor APG-5918. Highlights of the data on lisaftoclax presented at EHA 2024 are as follows: Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (Pts) with Relapsed or Refractory (R/R) Multiple Myeloma (MM) or Immunoglobulin Light-Chain (AL) Amyloidosis Abstract#: P917 Presentation Type: Poster presentation Topic: Myeloma and other monoclonal gammopathies – Clinical Date & Time: Friday June 14, 2024, 18:00 - 19:00 CEST Presenting Author: Prof. Sikander Ailawadhi, Mayo Clinic Florida Highlights: Background: R/R MM is incurable, with virtually inevitable relapse without appropriate therapeutic intervention. AL amyloidosis is a rare disease that may cause serious organ damage or death. Lisaftoclax is a novel, potent, selective BCL-2 inhibitor with clinical benefits in hematologic malignancies and solid tumors and a low reported incidence of adverse events (AEs). Introduction: The aim of this multicenter study was to evaluate the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Arms A and C) or daratumumab, lenalidomide, and dexamethasone (Arm B) in patients with R/R MM (Arms A and B) or R/R AL amyloidosis (Arm C). Patient enrollment and methods: Patients with an Eastern Cooperative Oncology Group (ECOG) performance status≤2 were administered lisaftoclax daily in repeated 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use. Dexamethasone was administered at 40 mg/day, and patients aged>75 were administered at the reduced dose of 20 mg/day. As of January 25, 2024, 44 patients that included 36 patients with R/R MM and 8 patients with R/R AL amyloidosis were enrolled in the 3 arms of the study (Arms A, B, and C) to receive lisaftoclax at various doses. The median (range) age of patients was 70.5 (24-88) years, 68.2% were male, and 65.9% were older than 65 years. The median (range) number of lines of prior therapies was 3 (1-19), median (range) time from diagnosis to the first dose of study drug was 5.5 (1-29) years, and median (range) number of treatment cycles was 4 (1-26). Efficacy results: In Arm A, 27 patients with R/R MM were efficacy evaluable. Among them, 10 had partial response (PR), 7 had very good PR (VGPR), and 2 had complete response (CR). The overall response rate (ORR [PR+VGPR+CR]) was 70.4%. In Arm B, 2 patients with R/R MM achieved CR. In Arm C, 7 patients with R/R AL amyloidosis were efficacy evaluable, and the ORR was 85.7% (4 VGPRs, 2 CR). Safety results: Of the 42 patients included in safety analysis, 10 patients experienced Grade ≥3 treatment-related adverse events (TRAEs), including neutropenia (14.3%), febrile neutropenia (2.4%). 3 patients experienced serious TRAEs that included febrile neutropenia, acute kidney injury, and diarrhea with electrolyte imbalance (1 each). A total of 24 patients discontinued treatment because of disease progression (n=15), treatment-emergent AE (TEAE, n=3), nonadherence (n=1), or investigator/patient decision (n=5). Conclusions: Lisaftoclax plus novel therapeutic regimens was well tolerated and demonstrated preliminary antitumor activity in patients with either R/R MM or AL amyloidosis. *Lisaftoclax is an investigational drug that has not been approved in any country and region. About Ascentage Pharma Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials, including 5 global registrational phase III studies, in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. SOURCE Ascentage Pharma

Orphan DrugClinical ResultFast TrackBreakthrough TherapyASH

18 Jun 2024

·www.biospace.com

GSK Reignites Blenrep Blockbuster Aspirations With Data from Phase III Studies

Pictured: GSK's office in Dresden, Germany/iStock, 13threephotography After a brief market exit in November 2022, GSK appears to be giving its multiple myeloma treatment Blenrep (belantamab mafodotin) a second chance, with company executives touting its “multi-blockbuster” potential in a virtual oncology-focused investor event on Monday. Much of GSK’s renewed enthusiasm for the antibody-drug conjugate (ADC) comes from promising data from two Phase III studies—DREAMM-7 and DREAMM-8—which saw strong signals of efficacy in Blenrep-based treatment regimens when used in multiple myeloma patients who had undergone at least one prior line of treatment. In DREAMM-7, which compared Blenrep against Johnson & Johnson’s Darzalex (daratumumab), GSK reported a “significant increase” in progression-free survival (PFS) in patients treated with the ADC. The Blenrep regimen resulted in a nearly 60% drop in the risk of disease progression or death versus Darzalex. The PFS benefit was statistically significant, with a p-value of less than 0.00001. In addition, median PFS in the Blenrep arm was 36.6 months, compared to those patients treated with Darzalex who only saw a median PFS of 13.4 months. The difference of approximately 23 months was “statistically significant and clinically meaningful,” according to GSK. At the time of analysis, Blenrep also showed an “early, strong, and clinically meaningful trend” toward better overall survival (OS) versus Darzalex. DREAMM-7 will continue its follow-up for OS. The Blenrep regimen also had superior depth of response than the Darzalex treatment, resulting in more than double the percentage of patients achieving at least complete response. Results from DREAMM-8—which compared a Blenrep-based regimen versus a corresponding treatment schedule that used Takeda’s Velcade (bortezomib)—were similarly promising. Patients treated with GSK’s ADC saw a “statistically significant and clinically meaningful” decrease in the risk of disease progression or death, which was almost 50% lower than in the Velcade group. Median PFS for Velcade treatment was 12.7 months, while it had not yet been reached at the time of analysis in the Blenrep patients. The Blenrep regimen also elicited deeper treatment responses than the Velcade schedule. More than twice the percentage of patients in the Blenrep arm achieved complete response or better than those treated with Velcade. Given these promising data, GSK Chief Commercial Officer Luke Miels estimated during Monday’s investor event that Blenrep could reach peak sales of more than $3 billion, driven mostly by the second-line opportunity in multiple myeloma. Blenrep could eventually dislodge Darzalex as the standard of care in this setting, Miels said. Blenrep, an ADC that targets the BCMA protein, was originally approved under the FDA’s accelerated pathway in August 2020. At the time, it was authorized as a monotherapy for relapsed or refractory multiple myeloma patients who had progressed after prior treatment with a proteasome inhibitor, anti-CD38 antibody and immunomodulatory agent. In November 2022, after falling short of its primary efficacy endpoint in its confirmatory Phase III trial DREAMM-3, GSK decided to pull Blenrep from the U.S. market. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Clinical ResultPhase 3Drug ApprovalImmunotherapyADC

17 Jun 2024

·www.fiercepharma.com

From market withdrawal back to £3B peak sales: GSK dreams big for myeloma ADC Blenrep

In second-line multiple myeloma, GSK’s goal is to replace Johnson & Johnson’s Darzalex with Blenrep, GSK Chief Commercial Officer Luke Miels said. Two back-to-back pivotal trial wins have rekindled hopes at GSK that once-failed multiple myeloma drug Blenrep could reach more than 3 billion pounds sterling in peak sales after all. GSK refloated that 3 billion-pound ($3.8 billion) figure during an oncology-focused investor event Monday. For an old calculation that had previously been thrown out following a market withdrawal in November 2022, GSK has maintained enough caution to still leave the non-risk-adjusted number out of its current group guidance. The 3 billion figure was mainly built on a potential FDA approval for Blenrep in second-line multiple myeloma, where GSK’s goal is to replace Johnson & Johnson’s Darzalex, GSK Chief Commercial Officer Luke Miels said on a separate call with reporters. In the phase 3 DREAMM-7 trial, Blenrep cut the risk of progression or death by 59% compared with Darzalex in the two meds’ respective combinations with Takeda’s Velcade and the steroid dexamethasone. It marked one of two positive second-line trials for the GSK drug. In the phase 3 DREAMM-8 study, Blenrep slashed the risk of cancer progression or death by 48% compared with Velcade in their respective combinations with Bristol Myers Squibb’s Pomalyst and dexamethasone. Miels suggested that as Darzalex, an anti-CD38 antibody, is increasingly used more in newly diagnosed patients, Blenrep, a BCMA-directed antibody-drug conjugate, could become a standard in the second-line setting. But Blenrep won’t be alone: J&J and Legend Biotech’s BCMA CAR-T Carvykti and potentially BCMA-targeted T-cell engagers such as J&J’s Tecvayli pose threats. During Monday’s press briefing, Miels once again highlighted CAR-T’s obstacle that requires these complicated therapies to be administered at a few specialized treatment centers when about 70% of myeloma patients in the U.S. are being treated in the community setting. While bispecifics can be given off the shelf outside large academic centers, patients still need to be hospitalized to monitor for potentially dangerous immune overreactions and neurologic symptoms with the drug’s current FDA-approved late-line label. Potentially fatal infections are another problem observed with the bispecifics. “I think we’ve got a very, very competitive product here that’s going to be compelling for community-based physicians—compelling for older, more frail patients,” Miels said. That distinction of an older population is important because doctors may also opt for combinations that use Amgen’s more potent proteasome inhibitor Kyprolis in younger, more fit patients. Neither CAR-T nor Blenrep has head-to-head data against Kyprolis-containing regimens. Blenrep has its own problem, notably eye toxicities. But Miels said the ocular problems are reversible and don’t lead to blindness. During the investor presentation, Evangelos Terpos, M.D., Ph.D., from the National & Kapodistrian University of Athens and principal investigator of the DREAMM-8 trial, noted that dose modifications in patients with ocular adverse events could still help patients achieve desirable outcomes while keeping treatment discontinuation rates low. “We’ve learned how to dose it in a way that we can reduce those risks for the patients and significantly reduce the number of patients that have to stop the drug,” Miels said on the press call, pointing to about 4% of patients in Blenrep’s phase 3 programs who had to discontinue treatment because of eye side effects. While the 3 billion-pound value is mostly pegged to the second-line setting, GSK is exploring the potential to move Blenrep into the first line. There, “we’ve just got to work out the dose and the design,” Miels said. When GSK made the decision to pull Blenrep off the market in late 2022 because of a phase 3 monotherapy flop, the British drugmaker decided not to downsize its 75-people-strong U.S. hematology commercial team. “Essentially, the calculated judgment we took at the time was that there would be a pathway back for Blenrep, because Blenrep is a very potent drug—it was really a question of dosing,” Miels said. The team is currently detailing GSK’s anemic myelofibrosis drug Ojjaara and are being trained around Blenrep. Miels said GSK will probably expand the sales team and the medical affairs team for Blenrep. For Ojjaara, GSK has pegged the JAK inhibitor to reach more than 1 billion pounds ($1.27 billion) in peak-year sales. The company also expects more than 2 billion pounds ($2.54 billion) at peak for the PD-1 inhibitor Jemperli, plus another 2 billion pounds for a package of candidates centered on the TIGIT antibody belrestotug. Blockbuster potential was also assigned to the B7-H3 and B7-H4 ADCs that GSK recently in-licensed from China’s Hansoh Pharma.

Phase 3Clinical ResultADC

100 Deals associated with Daratumumab

External Link

KEGG	Wiki	ATC	Drug Bank
D10777	Daratumumab	L01XC24	DB09331

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Immunoglobulin Light-Chain Amyloidosis	EU	Janssen-Cilag International NV	20 May 2016
Immunoglobulin Light-Chain Amyloidosis	IS	Janssen-Cilag International NV	20 May 2016
Immunoglobulin Light-Chain Amyloidosis	LI	Janssen-Cilag International NV	20 May 2016
Immunoglobulin Light-Chain Amyloidosis	NO	Janssen-Cilag International NV	20 May 2016
Multiple Myeloma	US	Janssen Biotech, Inc.	16 Nov 2015

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Residual Neoplasm	Phase 3	US	Janssen Research & Development LLC	26 Apr 2019
Residual Neoplasm	Phase 3	CA	Janssen Research & Development LLC	26 Apr 2019
Smoldering Multiple Myeloma	Phase 3	US	Janssen Research & Development LLC	06 Nov 2017
Smoldering Multiple Myeloma	Phase 3	CN	Janssen Research & Development LLC	06 Nov 2017
Smoldering Multiple Myeloma	Phase 3	CN	Xian Janssen Pharmaceutical Ltd.	06 Nov 2017
Smoldering Multiple Myeloma	Phase 3	JP	Janssen Research & Development LLC	06 Nov 2017
Smoldering Multiple Myeloma	Phase 3	AR	Janssen Research & Development LLC	06 Nov 2017
Smoldering Multiple Myeloma	Phase 3	AU	Janssen Research & Development LLC	06 Nov 2017
Smoldering Multiple Myeloma	Phase 3	BE	Janssen Research & Development LLC	06 Nov 2017
Smoldering Multiple Myeloma	Phase 3	BR	Janssen Research & Development LLC	06 Nov 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2024	Not Applicable	-	-	Daratumumab-based therapy with cyclophosphamide, bortezomib, and dexamethasone	xkiigemacq(lmvpwuvtfj) = uwujgfyird zwhoxbgubq (gmxobegejw ) View more	-	24 May 2024
				Daratumumab-based therapy with bortezomib and dexamethasone	xkiigemacq(lmvpwuvtfj) = sbozwgcgoe zwhoxbgubq (gmxobegejw ) View more
ASCO2024	Not Applicable	Plasma cell myeloma refractory anti-CD38 refractory	128	Dara-based retreatment (D2)	nvbgilsabb(pidwmpqydy) = gpwqkmiley ccqsomkczb (rchkkkquve ) View more	Positive	24 May 2024
NCT03710603 (PERSEUS, ASCO2024)	Phase 3	Multiple Myeloma Maintenance	709	DARA SC + VRd (D-VRd)	xtaybxkken(ihneinqmxc) = vmtzxlpfcp xmvnaiuvxn (bfwwroaise ) View more	Positive	24 May 2024
				VRd	xtaybxkken(ihneinqmxc) = rzbhbbyget xmvnaiuvxn (bfwwroaise ) View more
NCT03283917 (EHA2024) Manual	Phase 1	Immunoglobulin Light-Chain Amyloidosis	20	Daratumumab + Ixazomib+Dexamethasone	syekqtcveq(itvnbtndar) = vpacflzhae emhcegnlyf (yozdppkkrt ) View more	Positive	14 May 2024
NCT04131309 (EMN22, EHA2024) Manual	Phase 2	Immunoglobulin Light-Chain Amyloidosis First line	40	DARATUMUMAB	mdwjubpoqv(lkupzwwjft) = xbilrosjie idaplqmidn (gfgbsupkje, 48.2 - 77.6) View more	Positive	14 May 2024
NCT03283917 (EHA2024) Manual	Phase 1	Immunoglobulin Light-Chain Amyloidosis First line	20	Dexamethasone+ixazomib+DARATUMUMAB	(qmmqxlhtiv) = quqzuqujvs zaochqrjcv (lknpouybdj ) View more	Positive	14 May 2024
NCT02252172 (MAIA, EHA2024)	Phase 3	Multiple Myeloma	737	Daratumumab plus Lenalidomide and Dexamethasone (D-Rd)	fwvbfkkdfo(dlhgtqtfyr) = mszmzizpej ykwyyacgwr (lwxktqmbjf ) View more	Positive	14 May 2024
				Lenalidomide and Dexamethasone (Rd)	fwvbfkkdfo(dlhgtqtfyr) = ytqxppcbbs ykwyyacgwr (lwxktqmbjf ) View more
EHA2024	Not Applicable	-	-	Dara VTD	pmvatzsdlr(ysdlmsuyow) = qnnuoigpyh vhsplrqoxp (noonuqahrz ) View more	-	14 May 2024
				Dara VTD + bridging chemotherapy	pmvatzsdlr(ysdlmsuyow) = abvbbylmow vhsplrqoxp (noonuqahrz ) View more
EHA2024	Not Applicable	Relapse multiple myeloma 14;16 \| deletion 17p \| deletion TP53 ... View more	-	Daratumumab-lenalidomide-dexamethasone (DRd)	xxhjucehcn(xixgusxnzc) = djflitcgyn fotwnpijcx (kllrqrnjvu, 31.5 - 62) View more	Negative	14 May 2024
				daratumumab	xxhjucehcn(xixgusxnzc) = qfoigtzgpk fotwnpijcx (kllrqrnjvu ) View more
EHA2024	Not Applicable	Refractory Acute Leukemia CD38	10	Daratumumab-based regimen	ozrppaxcin(zwtovkzrqy) = btitgenros ysimvywbba (yealjavqml ) View more	Positive	14 May 2024
				Venetoclax in combination with the Dara regimen	ozrppaxcin(zwtovkzrqy) = fhxtweqvma ysimvywbba (yealjavqml ) View more

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