On December 5, 2020 Gracell Biotechnologies Inc. ("Gracell"), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported an interim readout to evaluate the safety and efficacy of its potential first-in-class GC012F FasTCAR-enabled dual-targeting BCMA/CD19 cell therapy in patients with relapsed or refractory multiple myeloma (R/R MM) (Press release, Gracell Biotechnologies, DEC 5, 2020, View Source [SID1234572264]). The data were presented by Dr. Weijun Fu, Professor of Hematology, Director at Shanghai Changzheng Hospital, as an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) 2020 Annual Meeting.

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GC012F, a dual BCMA/CD19 targeting CAR-T cell therapy developed on Gracell’s FasTCAR platform – which enables next-day manufacturing – was evaluated in an investigator-initiated Phase 1 trial. As of July 17th, the study enrolled sixteen patients at three dose levels with the highest dose level of 3×10^5 cells per kg. After three days of a standard lymphodepleting regimen, patients received GC012F as a single infusion over 30 minutes.

Early Overall Response Rate (ORR) showed a promising 93.7% with all responses being VGPR or better – showing fast, deep and durable responses in all dose levels
100% of the patients treated at the highest dose level (n=6) obtained a MRD negative sCR which was maintained through the landmark analysis of six months (n=4) at the time of data cut off
The median duration of follow up at time of assessment was 7.3 months (range 1–10 months). Of the sixteen patients treated, 93.7% were classified as high-risk according to mSMART 3.0 guidelines, 19% had double hit R/R MM, and 31% had extramedullary disease. Patients had received a median of 5 prior lines of therapy, with 75% being refractory to last therapy and 19% being primary refractory. 94% of the patients were triple exposed to a PI, IMiD, and at least a third treatment modality, including anti-CD38 targeted therapy. 63% were penta-exposed with at least five different treatment modalities, including PI, IMiD and others. One patient with extramedullary disease obtained MRD negative result at his first bone marrow assessment at month 1, however, he was considered a non-responder based on the increasing size of the extramedullary lesion at month 1.

The safety profile of GC012F was manageable with an overall low grade of cytokine release syndrome (CRS) (87.5 % Grade 1/2, 2 patients Grade 3, no Grade 4 or 5) and a median duration of four days ranging from 1–8 days. CRS was treated with Standard of Care treatment, including tocilizumab and steroids, and resolved in all cases. No ICANS (immune effector cell-associated neurotoxicity) was observed in any of the sixteen patients. Treatment-emergent adverse events (TEAEs) presented predominantly as cytopenias and AST increase. Lower respiratory tract infection was observed in three patients. All TEAEs were resolved with standard therapy.

"We are extremely encouraged about these early findings in sixteen patients with predominately high-risk features," said Dr. Martina Sersch, MD, PhD, CMO of Gracell. "High-risk patients are difficult to treat successfully and to achieve longer-term remission. A 100% MRD-sCR at month six post-infusion after treatment with GC012F at the highest dose level shows promise for heavily pretreated patients who have failed or were no longer responding to standard treatment options. We are planning to expand our program globally and are looking forward to sharing updates as we advance our programs through clinical development."

On December 5, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported initial data for the Phase 1 first-in-human dose escalation study of talquetamab (JNJ-64407564) for the treatment of relapsed or refractory multiple myeloma (NCT03399799) (Press release, Janssen Pharmaceuticals, DEC 5, 2020, View Source [SID1234572263]). Talquetamab is a first-in-class, and the only investigational bispecific antibody that targets both GPRC5D, a novel multiple myeloma target, and CD3 on T-cells. Initial results for both the subcutaneous (SC) and intravenous (IV) formulations show encouraging clinical activity against the GPRC5D target, which is highly expressed on multiple myeloma cells and associated with poor prognostic factors.1,2,3 At the SC recommended Phase 2 dose (RP2D), the overall response rate (ORR) was 69 percent (9/13) and 39 percent achieved a very good partial response (VGPR) or better. The data will be featured during the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting as an oral presentation on Saturday, December 5 at 5:00 p.m. ET (Abstract #290).

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"There is a pressing need for continued innovation of multiple myeloma treatments – particularly for patients who have relapsed on other therapies – and the results presented today for talquetamab are encouraging," said Ajai Chari, M.D., Professor of Medicine, the Director of Clinical Research in the Multiple Myeloma Program, and the Associate Director of Clinical Research, Mount Sinai Cancer Clinical Trials Office. "The Phase 1 overall response rate and safety profile support further study of talquetamab in monotherapy and in combination approaches for patients with few options for treatment."

Investigators identified the RP2D of 405 µg/kg SC and concluded subcutaneous treatment may provide an opportunity for less frequent dosing than the intravenous formulation. A response was observed in 6/9 triple-class refractory patients and 2/2 penta-drug refractory patients. Pharmacokinetic results indicate target exposure levels at the RP2D. At the RP2D of 405 µg/kg SC, pharmacodynamic data demonstrate consistent T-cell activation, cytokine production and redistribution.

Patients received talquetamab at doses of 1–180 µg/kg with IV administration and 5–800 µg/kg for the SC formulation. Results from the Phase 1 study showed responses in patients who were treated with talquetamab across dose groups; median time to first confirmed response across all doses was one month (range, 0.2–3).4

The Phase 1 study enrolled patients (n=157) with multiple myeloma who had progressed on, or could not tolerate, any available established therapies. Patients had received a median of six prior lines of treatment (range, 2-20); 87 percent were refractory to the last line of therapy, 82 percent were triple-class refractory, and 33 percent were penta-drug refractory to two or more immunomodulatory agents, two or more PIs, and an anti-CD38 therapy. The study is conducted in two parts: dose escalation (part 1) and dose expansion (part 2).4

In the Phase 1 study, adverse events (AEs) at the RP2D which occurred with a Grade 3 frequency of ≥25 percent among the SC cohort were neutropenia (42 percent). With SC dosing, cytokine release syndrome (CRS) was observed in 64 percent of patients and was low-grade with no Grade 3 or greater CRS events at the RP2D. CRS occurred at a median of two days after dosing, and median duration of CRS was also two days. The incidence of neurotoxicity was five percent at the RP2D, with no patients experiencing Grade 3 or greater events with SC dosing.4

"GPRC5D is a novel target in the treatment of multiple myeloma and, as a bispecific antibody that engages T-cells by also targeting CD3, talquetamab is emerging as a potential therapeutic option for heavily pretreated patients," said Yusri Elsayed, M.D., MHSc., Ph.D., Vice President, Global Head, Hematologic Malignancies, Janssen Research & Development, LLC. "Based on the preliminary efficacy, safety, pharmacokinetic and pharmacodynamic data presented today, we are committed to fully exploring the promise of talquetamab in multiple myeloma."

About Talquetamab
Talquetamab is a first-in-class investigational bispecific antibody targeting both GPRC5D, a novel multiple myeloma target, and CD3, the T-cell receptor.4 CD3 is involved in activating T-cells and GPRC5D is highly expressed on multiple myeloma cells.4,5,6 Results from preclinical studies in mouse models demonstrate that talquetamab induces T-cell-mediated killing of GPRC5D-expressing multiple myeloma cells through the recruitment and activation of CD3-positive T-cells and inhibits tumor formation and growth.6

Talquetamab is currently being evaluated in a Phase 1/2 clinical study for the treatment of relapsed or refractory multiple myeloma and is also being explored in combination studies. The development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody technology platform.*

*DuoBody is a registered trademark of Genmab A/S.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.7,8 When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow. In 2020, it is estimated that more than 32,000 people will be diagnosed and close to 13,000 will die from the disease in the U.S.9 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.10

On December 5, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported updated results from an ongoing Phase 1 first-in-human dose escalation study (NCT03145181) of teclistamab (JNJ-64007957) for the treatment of relapsed or refractory multiple myeloma (MM) (Press release, Janssen Pharmaceuticals, DEC 5, 2020, View Source [SID1234572251]). In heavily pretreated patients, the overall response rate (ORR) with teclistamab was 73 percent (16/22) at the recommended SC Phase 2 dose (RP2D).1 These results for the SC formulation support the recommended dose for the pivotal Phase 2 registration trial, which has started. In addition, updated results for the intravenous (IV) formulation demonstrate the durability of responses.1

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"The data presented today for the subcutaneous formulation build on promising results presented earlier this year for the intravenous regimen," said Alfred Garfall, M.D.,* Assistant Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, and presenting author. "The preliminary efficacy, including durability of responses, combined with the initial safety profile in this highly pretreated population is encouraging and supports further studies of teclistamab in patients with relapsed or refractory multiple myeloma who are in need of additional treatment options."

The study is conducted in two parts: dose escalation (part 1) and dose expansion (part 2), and enrolled patients with MM who had relapsed or were refractory to established therapies and had previously been treated with a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).1 Patients had received a median of six prior lines of treatment (range, 2-14); 96 percent were triple-class exposed, 81 percent were triple-class refractory, 91 percent were refractory to the last line of therapy, and 39 percent were penta-drug refractory (to two or more immunomodulatory agents, two or more PIs, and an anti-CD38 therapy).1 Prognosis is poor for patients with refractory MM as treatment options are limited.1

The RP2D was identified as 1500 µg/kg SC, and the maximum tolerated dose has not been identified. Fifty-five percent of patients achieved a very good partial response or better (12/22), and 23 percent of patients (5/22) achieved a complete response (CR) or better with RP2D SC dosing.1 After median follow-up of 3.9 months (range of 1.7–7.4 months), 94 percent (15/16) of responders treated with the SC RP2D were alive and progression-free.1 Responses appeared durable and deepened over time at the RP2D.1

Of the 11 patients who achieved CR and were evaluable for minimal residual disease (MRD) analysis across all IV and SC doses, eight patients attained MRD-negative CR at a threshold of 10-6 and one at a 10-5 threshold. Sustained MRD-negativity was confirmed for all five evaluable patients across the IV and SC cohorts.1

At the SC RP2D, 64 percent of patients experienced cytokine release syndrome (CRS) events, all of which were Grade 1 or 2 and generally confined to step-up, or a gradual increase in dosing, and first full doses.1 No patients discontinued treatment due to CRS. Of 33 treated patients at the RP2D, only one neurotoxicity event, which was reversible, was observed.1 Selection of the 1500ug/kg SC RP2D is supported by promising safety, efficacy, pharmacokinetics and pharmacodynamics. The SC formulation may provide an opportunity for less frequent dosing for patients than the IV formulation, although this has not been explored in the current study.1

The most common adverse events (AEs) (all grade ≥20 percent) for the RP2D in the SC cohort were CRS (64 percent); neutropenia (52 percent); anaemia (39 percent); thrombocytopenia (33 percent); leukopenia (33 percent); and fatigue (24 percent).1 In patients who experienced Grade 3 and above AEs (≥20 percent), the most common at the RP2D SC dose were neutropenia (33 percent); and anaemia (21 percent).1 One Grade 5 treatment related AE (pneumonia) was reported at the 80 µg/kg IV dose, but none at the RP2D.1

"We are committed to exploring treatment options that use promising modalities in multiple myeloma, including bispecific antibodies like teclistamab, that increase treatment responses through antigen targeting," said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Global Head, Hematologic Malignancies, Janssen Research & Development, LLC. "Our research in multiple myeloma is broad, exploring multiple targets through a variety of approaches. We continue to identify new treatment options, particularly for patients who have relapsed or become refractory to existing therapies."

"These initial results demonstrate the early promise of bispecific antibodies for people living with multiple myeloma and may, in the future, provide healthcare professionals with another tool in their arsenal to treat this devastating disease." said Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "Their development builds on our rich heritage in multiple myeloma, where we have continually sought to investigate new treatment strategies that have the potential to address remaining unmet needs."

Additional pharmacokinetic and ex vivo data for teclistamab will be highlighted in a poster on Monday, December 7 from 4:00pm to 12:30am CET (Abstract #3194).2 This study evaluated the ability of teclistamab to induce cytotoxicity and T-cell activation.2

*Alfred Garfall is lead investigator of the NCT03145181 study and was not compensated for any media work

#ENDS#

About Teclistamab
Teclistamab is an investigational bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3. BCMA is expressed at high levels on multiple myeloma cells.3,4,5,6,7 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce cytotoxicity of the targeted cells.5,6 Results from preclinical studies demonstrate that teclistamab kills myeloma cell lines and bone marrow-derived myeloma cells from heavily pretreated patients.6

Teclistamab is currently being evaluated in a Phase 2 clinical study for the treatment of relapsed or refractory multiple myeloma (NCT04557098) and is also being explored in combination studies (NCT04586426, NCT04108195). The production and development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody technology platform.** In October and November 2020, the European Commission and the U.S. Food and Drug Administration (FDA), respectively, granted teclistamab orphan designation for the treatment of multiple myeloma.8,9

**DuoBody is a registered trademark of Genmab A/S.

About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.10 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.11 Around 50 percent of newly diagnosed patients do not reach five-year survival,12,13 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.14

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.15 Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course.16 While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.17 Patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.18

On December 5, 2020 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that new safety and efficacy findings from the expansion phase of the Phase 1/2 study of IMGN632 in patients with relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN) were presented during an oral session at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, ImmunoGen, DEC 5, 2020, View Source [SID1234572250]).

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"Comprising the largest prospective study with a single agent in patients with relapsed/refractory BPDCN, the results presented at ASH (Free ASH Whitepaper) build on the previous data reported for IMGN632 and reinforce the potential of this CD123-targeting ADC as a best-in-class treatment option for BPDCN," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "Given IMGN632’s favorable safety profile, demonstrated anti-tumor activity, and ease of administration via short infusion in an outpatient setting, we continue to enroll both frontline and relapsed/refractory BPDCN patients in this trial. In addition, the preclinical data presented by our partners at MD Anderson Cancer Center in relapsed/refractory AML further support the combination of IMGN632 with azacitidine and venetoclax, which we are actively enrolling in a Phase 1b/2 clinical trial."

"BPDCN is a rare, aggressive hematologic malignancy that is characterized by historically low overall survival rates," said Naveen Pemmaraju, MD, Associate Professor in the Department of Leukemia at MD Anderson Cancer Center. "Despite currently available therapies, outcomes for relapsed/refractory patients remain poor and there is an urgent need to develop better-tolerated treatment options in the frontline setting. These updated safety and efficacy findings for IMGN632 in patients with relapsed/refractory BPDCN are encouraging, and I look forward to advancing IMGN632 into pivotal development."

IMGN632 MONOTHERAPY DATA IN BPDCN

Title: "Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, in Patients with Relapsed/Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm" (Abstract #167)

Oral Presentation Session: 616
Date: Saturday, December 5, 2020
Time: 12:30pm PT/3:30pm ET
Updated key findings include:

Safety

IMGN632 demonstrated a favorable safety profile in 29 patients who received 0.045 mg/kg once every 3 weeks via a short (under 30 minutes) intravenous infusion, with limited grade ≥3 treatment-related adverse events (AEs) and no treatment-related deaths.
The most common grade ≥3 AEs were febrile neutropenia, hyperglycemia, and thrombocytopenia (10% each).
Grade ≥3 liver function test elevations were seen in one patient (3%).
No capillary leak syndrome was reported.
Efficacy

In all relapsed/refractory BPDCN patients, the overall response rate (ORR) was 29% (8/28) with a composite complete remission (CCR) rate of 18% (5/28).
In patients with prior SL-401 exposure (tagraxofusp-erzs), the ORR was 31% (4/13) with a CCR of 15% (2/13).
Among patients with bone marrow response assessment, 60% (9/15) achieved a bone marrow complete response (blasts <5%).
Durable responses were seen in multiple patients, up to 9.2 months without hematopoietic stem cell transplant.
Two patients have been successfully bridged to hematopoietic stem cell transplant.
TRIAL IN PROGRESS POSTER

Title: "A Phase 1b/2 Study of IMGN632, a CD123-Targeting Antibody-Drug Conjugate, As Monotherapy or in Combination with Venetoclax and/or Azacitidine for Patients with CD123-Positive Acute Myeloid Leukemia" (Abstract 1047)
Poster Session: 616
Date: Saturday, December 5, 2020
Time: 7:00am – 3:30pm PT/10:00am – 6:30pm ET

PRECLINICAL POSTER

In addition, our partners at MD Anderson Cancer Center will present preclinical data from their study combining IMGN632, venetoclax, and azacitidine in in vitro and in vivo AML models.

Title: "Combining IMGN632, a Novel CD123-Targeting Antibody Drug Conjugate with Azacitidine and Venetoclax Facilitates Apoptosis in Vitro and Prolongs Survival In Vivo in AML Models" (Abstract 2886)
Poster Session: 617
Date: Monday, December 7, 2020
Time: 7:00am – 3:30pm PT/10:00am – 6:30pm ET

Additional information can be found at www.hematology.org, including abstracts.

CONFERENCE CALL INFORMATION

ImmunoGen will hold a conference call on Monday, December 7 at 8:00 a.m. ET to discuss the data presented at ASH (Free ASH Whitepaper), the pathway to FDA approval in BPDCN, and an AML program progress update; Dr. Naveen Pemmaraju, Associate Professor in the Department of Leukemia at MD Anderson Cancer Center, will join the call to review the BPDCN data presented at ASH (Free ASH Whitepaper). To access the live call by phone, dial (877) 621-5803; the conference ID is 1795760. The call, along with associated slides, may also be accessed through the Investors and Media section of immunogen.com. Following the call, a replay will be available at the same location.

ABOUT IMGN632

IMGN632 is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and acute lymphocytic leukemia (ALL). IMGN632 is currently being evaluated in multiple cohorts, including monotherapy for patients with BPDCN and minimal residual disease positive (MRD+) AML following frontline induction therapy and in combinations with Vidaza (azacitidine) and Venclexta (venetoclax) for patients with relapsed/refractory AML. IMGN632 uses one of ImmunoGen’s novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA without crosslinking. IGNs have been designed to have high potency against tumor cells, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads. FDA has granted IMGN632 Breakthrough Therapy Designation in relapsed/refractory BPDCN.

ABOUT BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)

BPDCN is a rare form of blood cancer that has features of both leukemia and lymphoma, with characteristic skin lesions, lymph node involvement, and frequent spread to the bone marrow. This aggressive cancer requires intense treatment often followed by stem cell transplant. Despite the approval of a CD123-targeting therapy, the unmet need remains high for patients, both in the frontline and in the relapsed/refractory setting.

ABOUT ACUTE MYELOID LEUKEMIA (AML)

AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems, and anemia. It is estimated that, in the U.S. alone, 21,380 patients will be diagnosed with AML this year and 10,590 patients will die from the disease.

ABOUT CD123

CD123, the interleukin-3 alpha chain, is expressed on multiple myeloid and lymphoid cancers including AML, BPDCN, ALL, chronic myeloid leukemia, and myeloproliferative neoplasms. With limited expression on normal hematopoietic cells, rapid internalization, and expression on AML leukemia stem cells, CD123 is a validated therapeutic target, with the approval of a CD123-targeting therapy for BPDCN.

On December 5, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reportedlonger-term results from the combined Phase 1b/2 CARTITUDE-1 study (NCT03548207) evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), an investigational B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Janssen Pharmaceuticals, DEC 5, 2020, View Source [SID1234572249]). These data, presented as an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting (Abstract #177), continued to demonstrate a very high overall response rate of 97 percent, which deepened over time with 67 percent of patients achieving a stringent complete response.1 With a median follow-up of 12.4 months, median duration of response and progression-free survival (PFS) were not reached.1

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"Unfortunately, for patients with multiple myeloma for whom at least three established treatment regimens have stopped working, the prognosis is often not good," said Deepu Madduri,* M.D., Assistant Professor of Medicine, Hematology and Medical Oncology, The Tisch Cancer Institute at Mount Sinai, New York, and principal study investigator. "In the CARTITUDE-1 study, heavily pretreated patients, including those who were triple-class refractory, achieved an impressive response following a single infusion of ciltacabtagene autoleucel."

Median time to first response was one month (range, 0.9-8.5), with responses observed at a low dose of CAR-T cells (median administered dose 0.71×106 CAR+ viable T cells/kg) and were ongoing in 72 percent (n=70) of patients. Additionally, 93 percent of evaluable patients (n=53) achieved minimal residual disease (MRD) negative disease status at 10-5.1 The trial included heavily pretreated patients, with evaluated patients having received a median of six prior treatment regimens (range, 3-18); 88 percent (n=85) were triple-refractory, 42 percent (n=41) were penta-refractory, and 99 percent (n=96) were refractory to the last line of therapy.1 The 12-month PFS rate was 77 percent (95 percent confidence interval [CI], 66-84).1 The 12-month overall survival (OS) rate was 89 percent (95 percent CI, 80-94) and manufacturing of cilta-cel was successful for all patients.1

"The combined Phase 1b/2 data from the CARTITUDE-1 study include a larger patient population than previously reported in the initial Phase 1b results, and we are encouraged that patients treated with cilta-cel continued to achieve impressive, deep responses," said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research Development, Janssen Research & Development, LLC. "The responses also appeared to be durable as indicated by the estimate that 89 percent of patients remained alive and 77 percent of patients remained progression-free after one year of follow up."

"We are committed to applying the best science and disease insights to bring transformational therapies for people living with blood cancers," adds Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "We are excited to see these latest results reinforce the early promising data previously presented and hope that one day cilta-cel can offer a viable treatment option for multiple myeloma patients who have limited therapeutic options."

In these combined results, the most common haematologic adverse events (AEs) observed in the CARTITUDE-1 study were neutropenia (96 percent); anemia (81 percent); thrombocytopenia (79 percent); leukopenia (62 percent); and lymphopenia (53 percent).1 Cytokine release syndrome (CRS) of any grade was observed in 95 percent of patients, with a median duration of four days (range, 1-97), and 99 percent of which were resolved within 14 days of onset.1 Of the 92 patients with CRS, 95 percent (n=87) were Grade 1/2, three percent (n=3) were Grade 3, one percent (n=1) was Grade 4 and one percent (n=1) was Grade 5.1 The median onset of CRS was at seven days (range, 1-12) post-infusion, with 89 percent (n=82) of patients experiencing CRS onset at day four or later.1

Neurotoxicity of any grade was observed in 21 percent (n=20) of patients, with Grade 3 or higher neurotoxicity observed in 10 percent (n=10) of patients.1 Of these, Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed in 16 patients; other neurotoxicities were observed in 12 patients and generally occurred after resolution of CRS and/or ICANS.1 ICANS events were resolved in all patients with a median time to recovery of four days (range, 1-12).1 Other neurotoxicities were resolved in six patients with a median time of 75 days (range, 2-160) and were not resolved in six patients (one with ongoing toxicity, one died from neurotoxicity and four died due to other causes).1 Fourteen deaths were reported during the study: five due to disease progression, three due to adverse events unrelated to treatment (acute myelogenous leukemia (n=2), pneumonia (n=1)) and six due to adverse events related to treatment (sepsis and/or septic shock (n=2), CRS/ hemophagocytic lymphohistiocytosis (n=1), lung abscess (n=1), respiratory failure (n=1) and neurotoxicity (n=1)).1

*Deepu Madduri is the lead investigator of the CARTITUDE-1 study. She was compensated for media work during the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting

#ENDS#

About CARTITUDE-1
CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicentre study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory multiple myeloma, 99 percent of whom were refractory to the last line of treatment; 88 percent of whom were triple-class refractory, meaning their cancer did not, or no longer responds to an immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody.1,2

The primary objective of the Phase 1b portion of the study, involving 29 patients, was to characterise the safety and confirm the dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2).2 Based on the safety profile observed in this portion of the study.1 The Phase 2 portion of the study, is evaluating the efficacy of cilta-cel with overall response as the primary endpoint.1

About Ciltacabtagene Autoleucel (cilta-cel)
Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy for the treatment of patients with multiple myeloma. The design comprises a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies.1 CAR-T cells are an innovative approach to eradicating cancer cells by harnessing the power of a patient’s own immune system.3 BCMA is a protein that is highly expressed on myeloma cells.4

In December 2017, Janssen entered into an exclusive worldwide license and collaboration agreement with Legend Biotech to develop and commercialise cilta-cel.5 In May 2018, Janssen initiated a Phase 1b/2 CARTITUDE-1 trial (NCT03548207) to evaluate the efficacy and safety of cilta-cel in adults with relapsed and/or refractory multiple myeloma, informed by the LEGEND-2 study results.2

In April 2019, cilta-cel was granted PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA).6 PRIME offers enhanced interaction and early dialogue to optimise drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.7 In February 2020, the European Commission granted orphan designation for cilta-cel.8

About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.9 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.10 Around 50 percent of newly diagnosed patients do not reach five-year survival,11,12 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.13

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.14 Refractory MM is when a patient’s disease progresses within 60 days of their last therapy.15 Relapsed cancer is when the disease has returned after a period of initial, partial or complete remission.15 While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.16 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.17