On December 12, 2021 IASO Biotherapeutics ("IASO Bio"), a clinical-stage biopharmaceutical company focused on discovering, developing, and manufacturing innovative medicines and Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported the latest data from the phase 1/2 clinical study of a fully human B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy in an oral presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Abstract # 547) (Press release, IASO Biotherapeutics, DEC 12, 2021, View Source [SID1234596873]). BCMA CAR-T therapy was co-developed by the two companies (IASO Bio: CT103A, Innovent: IBI326) for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). Presentation title: A Phase 1/2 Study of a Novel Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT103A) in Patients with Relapsed and/or Refractory Multiple Myeloma with Professor Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) in China as the oral presenter.

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The updated data is based on a single-arm, open-label, multi-center phase 1/2 study being conducted in China. The study mainly enrolled patients with BCMA-positive RRMM who had an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 and received ≥3 lines of prior therapy. The study’s primary endpoint is objective response rate (ORR), with secondary endpoints including duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD). As the data cutoff date of Oct.12, 2021, this study included 79 subjects treated with the recommended Phase II dose (RP2D) of 1.0×106 CAR-T cells/kg (9 from the exploratory investigator-initiated trial [IIT] and 70 from the registrational study [Trial Registration# NCT05066646]).

Study results showed that CT103A has excellent safety and efficacy profiles, as corroborated by long in vivo persistence, indicating that CT103A has the potential to be a breakthrough therapy for patients with RRMM.

CT103A demonstrated a favorable and manageable safety profile: Among the 79 patients, 75 (94.9%) experienced cytokine release syndrome (CRS). The majority of them experienced 1~2 CRS; only 2 experienced grade 3 CRS (all occurred during the IIT phase of the study, while the 70 patients in the registrational study did not report any grade 3 or higher CRS). The median time to CRS onset was 6.0 days after infusion, and the median duration of CRS was 5.0 days. Only 1 patient experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) manifested as transient decrease in consciousness and soon resolved without intervention. All patients with CRS or ICANS have resolved, among which 20% and 34.7% were treated with tocilizumab and steroids respectively.

CT103A showed favorable and durable efficacy: Of the 79 patients, the ORR was 94.9% and the complete response/stringent complete response (CR/sCR) rate was 58.2%, with a trend suggesting a correlation between deeper responses and longer follow-ups. PFS at 6, 9, and 12 months after infusion was 78.0%, 76.0%, and 71.0%, respectively. CT103A also demonstrated favorable efficacy in 11 patients with EMM, achieving an ORR of 100% and a CR/sCR rate of 72.7%. In all 79 patients, 93.7% achieved minimal residual disease (MRD)-negativity with a sensitivity of 10-5 at least once after infusion.

CT103A also demonstrated favorable efficacy in patients who had received prior CAR-T therapy: Among the 13 patients who previously received CAR-T therapy, the ORR was 76.9%, with 61.5% of those patients achieving very good partial response (VGPR) or deeper responses, and 46.2% achieved CR/sCR.

CT103A demonstrated robust expansion and prolonged persistence: The expansion of CT103A in peripheral blood reached the peak at a median of 12 days, with a median Cmax of 92,000 copies/ug DNA. CT103A was still detectable in 10 (55.6%) of the 18 patients who completed 12-month follow-up after infusion. The first enrolled patient still had detectable CT103A transgene (4,040 copies/ug DNA) 34 months (1,030 days) after infusion, and remained in sCR during this time. Soluble BCMA in peripheral blood of patients rapidly declined after CT103A infusion and persistently remained below the detectable limit.

CT103A has low immunogenicity: Only 1.3% (1/79) of patients were tested anti-drug antibody (ADA)-positive within three months after CT103A infusion. At a median follow-up duration of seven months, only 12.7% (10/79) of patients tested ADA-positive.

"While a high rate of relapse remains a major clinical challenge in RRMM, BCMA-targeted CAR-T has thus far showed great promise in its treatment. CT103A is a fully-human BCMA-specific CAR-T therapy that can reduce relapse by bypassing potential anti-CAR immunogenicity in the host. This CT103A study demonstrated favorable efficacy, safety, PK/PD, and low immunogenicity, signifying enormous therapeutic value for the treatment of RRMM as potentially a clinical breakthrough," said the two principal investigators at the primary centers of the study – Prof. Lugui Qiu, MD, from the Chinese Academy of Medical Science Hematology Hospital and Prof. Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.

Dr. Wen (Maxwell) Wang, Chief Executive Officer and Chief Medical Officer of IASO Bio, said: "This is our second time reporting CT103A results during an oral session at ASH (Free ASH Whitepaper) Meeting. And this year’s new data for safety and efficacy of CT103A is particularly exciting. It includes some of the results from the registrational study at 11 sites which is worth emphasizing since it’s globally the first registrational study that enrolled patients who had failed prior CAR-T treatment. For these patients, who have no approved treatment options, CT103A also demonstrated favorable and durable efficacy, once again highlighting the enormous therapeutic potential of this innovative candidate. At present, we are also advancing the clinical development of CT103A for early-line treatments, combination therapies and autoimmune diseases, while expanding the development program globally. We’ll submit the new drug application (NDA) soon and look forward to launching this cell therapy to benefit even more patients in the future. "

Dr. Hui Zhou, Senior Vice President of Innovent, said: "Multiple myeloma (MM) is a common hematology malignant disease with high incidence rate, and relapse and refractory are inevitable after current treatments. There’s an urgent unmet need requesting a treatment with well-tolerated and long persistence for patients. We are glad the results from the Phase I/II study of CT-103A (Innovent R&D code: IBI326) were announced in an oral presentation at this year’s ASH (Free ASH Whitepaper) Annual Meeting. These results looks very promising as they have demonstrated favorable and durable efficacy and manageable efficacy of IBI326. We will further accelerate this clinical development of IBI326 to bring forth a treatment option that will bring new hope to patients with MM."

About Multiple Myeloma (MM)
Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For multiple myeloma patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there’s currently no cure. As a result, there is a significant unmet need for patients with relapsed/refractory multiple myeloma. In the United States, MM accounts for nearly 2% of all cancer cases, and more than 2% of cancer-related deaths.

According to Frost & Sullivan, the number of new MM cases in the United States rose from 30,300 in 2016 to 32,300 in 2020 and is expected to increase to 37,800 by 2025. The total number of patients diagnosed with MM in the United States increased from 132,200 in 2016 to 144,900 in 2020 and is expected to rise to 162,300 by 2025.

The number of new MM cases in China rose from 18,900 in 2016 to 21,100 in 2020 and is expected to increase to 24,500 by 2025. The total number of patients diagnosed with MM in China increased from 69,800 in 2016 to 113,800 in 2020 and is expected to rise to 182,200 by 2025.

About CT103A (BCMA CAR-T)
CT103A is an innovative therapy co-developed by IASO Bio and Innovent Biologics. Previous studies indicate subjects with relapsed/refractory multiple myeloma (RRMM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells will not be effective. To solve this dilemma, CT103A has been developed, a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3ζ activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform and integrated in house manufacture process improvement, the construct of the BCMA CAR-T is potent and CT103A shows prolonged persistency in patients. In February 2021, CT103A was granted Breakthrough Therapy Designation (BTD) by China’s National Medical Products Administration (NMPA) for the treatment of RRMM. In addition to multiple myeloma, IASO Bio is investigating CT103A in patients with autoimmune diseases.

On December 12, 2021 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported that new preclinical data supporting the safety and efficacy profile of WU-CART-007 for T-cell malignancies (Press release, Wugen, DEC 12, 2021, View Source [SID1234596862]). Further, today’s data highlighted Wugen’s clinical readiness and robust manufacturing process for WU-CART-007. The U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for WU-CART-007 and Wugen is preparing for enrollment of a Phase 1/2 clinical trial for relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (LBL) (NCT#04984356).

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WU-CART-007 is an off-the-shelf, fratricide-resistant CD7-targeted CAR-T cell therapy designed to overcome the technological challenges of harnessing CAR-T cells to treat CD7+ hematological malignancies. Wugen is deploying CRISPR/Cas9 gene editing technology to delete CD7 and the T-cell receptor alpha constant (TRAC), preventing CAR-T cell fratricide and mitigating the risk of graft-versus-host-disease (GvHD). WU-CART-007 is manufactured using healthy donor-derived T-cells to eliminate the risk of malignant cell contamination historically observed in the autologous CAR-T setting.

"Adult and pediatric patients with T-cell malignancies experience high rates of relapse and mortality," said Dan Kemp, Ph.D., President and Chief Executive Officer of Wugen. "We believe WU-CART-007 is the first off-the-shelf allogeneic CAR-T cell therapy targeting this category of hematological cancers to receive an IND clearance from the FDA, and our program has tremendous potential to address this critical unmet need for patients. Today’s preclinical data validate our approach and support the clinical advancement of WU-CART-007. We look forward to enrolling patients in our Phase 1/2 clinical trial to evaluate WU-CART-007 in R/R T-ALL and LBL."

Key findings reported in the poster include:

Wugen has developed a robust manufacturing process to enable clinical development of WU-CART-007, using healthy donor-derived T-cells to eliminate the risk of malignant cell contamination, and CRISPR/Cas9 gene editing to prevent fratricide and mitigate the risk of GvHD.
WU-CART-007 models primarily a T-cell central memory phenotype with enhanced functionality.
WU-CART-007 exhibits strong CD7-specific anti-tumor activity in vitro and in vivo, with a favorable off-target profile.
Robust pre-clinical data support clinical development of WU-CART-007 in CD7+ hematological malignancies. A Phase 1/2 clinical trial evaluating WU-CART-007 in patients with R/R T-ALL/LBL will open for enrollment in December 2021.

On December 12, 2021 Epizyme, Inc. (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering transformative therapies against novel epigenetic targets, reported that updated safety and activity data from the Phase 1b portion of its Phase 1b/3 confirmatory study evaluating the investigational use of TAZVERIK (tazemetostat), a first-in-class, oral, selective inhibitor of EZH2, in combination with rituximab + lenalidomide (R2) in patients with relapsed/refractory follicular lymphoma (FL) who have been treated with at least one prior systemic therapy, including patients who are rituximab-refractory and/or POD24, at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Epizyme, DEC 12, 2021, View Source [SID1234596859]).

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Updated data from the Phase 1b portion of the study reported today included 40 FL patients who had received treatment with tazemetostat and R2 (400 mg [n=4], 600 mg [n=18], or 800 mg [n=18]) as of the September 29, 2021 data cut-off. The findings demonstrated that the safety profile of the tazemetostat and R2 combination was consistent with the previously reported safety information in the prescribing information for both tazemetostat and R2, respectively. Additionally, there was no clear dose response for treatment-emergent adverse events (TEAEs) or dose modifications. Thirty-five of the 40 patients were evaluable for tumor assessments as of the data cut off, with 32 patients responding to treatment. The activity findings showed an objective response rate of 91.4 percent (37.1 percent complete response rate and 54.3 percent partial response rate). The duration of response data continue to mature as the study is ongoing.

"The data presented today on the combination of rituximab, lenalidomide and tazemetostat, known as R2 + tazemetostat, have shown promising responses in the second-line FL setting and the side effects observed to date have been consistent with lenalidomide-based combinations," said Connie Lee Batlevi, MD PhD, medical oncologist with Memorial Sloan Kettering Cancer Center. "We are excited to start the randomized Phase 3 portion of the study, with the hope of developing a chemotherapy-free combination regimen for patients with follicular lymphoma."

SYMPHONY-1 (EZH-302) is an international, multicenter, randomized, double-blind, active-controlled, 3-stage, biomarker-enriched, confirmatory Phase 1b/3 study, which is designed to evaluate the safety and efficacy of tazemetostat in combination with R2 in patients with relapsed or refractory FL after at least one prior line of therapy. The Phase 1b portion of the study is designed to determine the recommended Phase 3 dose, activity, and safety of tazemetostat and R2. In addition to the safety run-in analysis, the study also assessed the pharmacokinetics and continues to assess clinical activity of tazemetostat when administered in combination with R2.

The Phase 1b safety run-in component evaluated tazemetostat at three dose levels (400 mg, 600 mg, and 800 mg orally twice daily) in 28-day cycles with standard-dose R2 using a 3 + 3 design. Rituximab was administered at 375 mg/m2 intravenously on days 1, 8, 15 and 22 of cycle 1, then on day 1 of cycles 2 to 5. Lenalidomide was administered at 20 mg (creatinine clearance ≥60 mL/min) or 10 mg (if creatinine clearance <60 mL/min) orally once daily on days 1 to 21 every 28 days for 12 cycles. In the Phase 3 component, approximately 500 patients will be randomly assigned to receive the RP3D of tazemetostat + R2 or placebo + R2. The study will also include a maintenance arm with tazemetostat or placebo following the first year of treatment with tazemetostat + R2 or placebo + R2.

Treatment with tazemetostat and R2 was generally well tolerated. Grade 3/4 TEAEs were observed in 17 (42.5%) patients; the most common grade 3/4 TEAE (≥10%) was neutrophil count decrease/neutropenia (15.0.%) Ten patients (25.0%) reported a total of 16 SAEs (serious adverse events). The only SAE reported in >1 patient was COVID-19, reported in 2 patients; all other SAEs were reported in 1 patient each.

A table of the activity findings as of the data cut off are below:

Best Overall Response (BOR) Ratea, n (%)

Tazemetostat + R2 (n = 35)

Objective Response Rate (ORR)

32 (91.4)

Complete Responseb (CR)

13 (37.1)

Partial Response (PR)

19 (54.3)

Stable Disease (SD)

3 (8.6)

Progressive Disease (PD)

0

a For BOR, there were 27 PET-CT-based responses and 8 CT-based responses.

b For CR, 12 were PET-CT-based responses and 1 was a CT-based response.

"We are encouraged to share progress of our tazemetostat program in follicular lymphoma with the cancer community, as we believe these data support the potential tazemetostat may play as a backbone of therapy in combination with current standards of care for patients living with the disease. We will continue to monitor these patients and we look forward to sharing follow-up data as they mature over time," said Dr. Shefali Agarwal, Executive Vice President and Chief Medical and Development Officer at Epizyme. "At Epizyme, we are committed to advancing the follicular lymphoma treatment landscape for patients, the healthcare teams who treat them, and the families who support them."

In addition to the SYMPHONY-1 presentation (Abstract #2207), two additional tazemetostat studies are being presented during the ASH (Free ASH Whitepaper) Annual Meeting. The first is a trial-in-progress/study design presentation for SYMPHONY-2 (Abstract #3541), a multi-center, open-label, single-arm, Phase 2 study of tazemetostat in combination with rituximab for the treatment of relapsed or refractory FL. The trial is actively enrolling patients across 18 sites in the United States. The second presentation (Abstract #1183) focuses on the analysis of the molecular and genetic characterization of patients treated with tazemetostat to better understand the drivers of response to treatment.

About TAZVERIK (tazemetostat)

TAZVERIK is a methyltransferase inhibitor indicated for the treatment of:

Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

View the U.S. Full Prescribing Information here: Epizyme.com

On December 12, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported updated data from its Phase 1 dose-escalation study of plamotamab, a CD20 x CD3 bispecific antibody, in patients with B-cell non-Hodgkin lymphomas (Press release, Xencor, DEC 12, 2021, View Source [SID1234596832]). Data will be presented by Krish Patel, M.D., Director of the Lymphoma Program at Swedish Cancer Institute, in a poster session today from 6:00 p.m. to 8:00 p.m. EST at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia.

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"Plamotamab is generally well tolerated and demonstrates encouraging clinical activity in heavily pretreated patients at our recommended intravenous Phase 2 dose of 50 mg flat dosing every two weeks following step-up dosing. Additionally, our pharmacokinetic modeling supports subcutaneous administration, which we plan to incorporate next year into our ongoing Phase 1 monotherapy study," said Allen Yang, M.D., Ph.D., senior vice president and chief medical officer at Xencor. "We are especially encouraged that these results support the potential for a differentiated safety profile and better outcomes for patients when plamotamab is combined with other agents in a chemotherapy-free regimen. To that end, early next year we will initiate the first combination study, with tafasitamab and lenalidomide, in patients with relapsed or refractory diffuse large B cell lymphoma. Additionally, our new worldwide collaboration with Janssen for advancing plamotamab development expands our strategy to develop multiple highly active chemotherapy-free regimens across B-cell cancers, importantly with tumor-selective, co-stimulatory CD28 bispecific antibodies."

Study Design

The Phase 1 study of plamotamab was originally designed in two parts: Part A to establish an initial priming dose with fixed, weight-based dosing regimens and Part B to escalate dosing on administrations after the priming dose (doses between 80 and 360 mcg/kg). A third part, Part C, was added to establish a step-up dosing regimen with higher, flat and less frequent dosing.

The Part C schedule, an intravenous, 50 mg flat dose every two weeks after step-up dosing during the first two cycles of treatment, was generally well tolerated and was determined to be the recommended Phase 2 dose.

Expansion cohorts are actively recruiting patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and are dosing using the recommended Phase 2 regimen to further evaluate the safety and efficacy of plamotamab monotherapy.

Safety Analysis

The safety population included 50 patients in Part B (38 DLBCL, 12 FL) and 14 patients in Part C (8 DLBCL, 4 FL, 1 marginal zone lymphoma, 1 mantle cell lymphoma). Patients were heavily pretreated, had a median age of 61.5 years, had a median of 4 prior therapies and had been diagnosed a median of 26.5 months prior to treatment.

In Part C of the study, patients had generally more advanced disease and poorer responses to prior therapy. The Part C population had a median age of 64 years, had a median of 5 prior therapies and had been diagnosed a median of 30.5 months prior to treatment. Of the 14 patients in Part C, eight patients received prior CAR-T and three patients received NK cell therapy. Two of these patients received both. All eight patients with DLBCL received prior CAR-T therapy.

The most common Grade 3 or 4 treatment-emergent adverse events (AEs) across all patients were anemia (21%), neutropenia (19%), hypophosphatemia (11%), thrombocytopenia (11%) and lymphopenia (10%). Four patients (5%) experienced Grade 3 or 4 cytokine release syndrome (CRS), each instance on the first dose, and no patients experienced Grade 3 or 4 CRS in Part C of the study. The rate of CRS of any grade fell from 74% in Part B to 57% in Part C. CRS was generally manageable with premedication.

In Part C, safety events were generally mild or moderate in severity. Grade 3 or 4 AEs experienced by more than 5% of patients included anemia (14%), lymphopenia (14%) and one patient each (7%) experiencing neutropenia, thrombocytopenia, decreases in neutrophil count, transaminase increases, fatigue and gamma-glutamyl transferase increases. Nervous system events did not lead to discontinuations, and no related neurotoxicity greater than Grade 2 was observed.

Efficacy Analysis

The efficacy analysis included 47 evaluable patients with either DLBCL or FL who were treated in Part B (n=38) or in Part C (n=9). Responses were assessed based on the Lugano Classification. The objective response rate (ORR) was 51% (24/47), and complete responses (CR) were observed in 12 patients (26%).

In part C of the study, the ORR was 100% (4/4) for patients with follicular lymphoma (FL), and CRs were observed in two patients (50%). For patients with diffuse large B-cell lymphoma, the ORR was 40% (2/5), and a CR was observed in one patient (20%). All 5 evaluable patients with DLBCL received prior CAR-T therapy, and two evaluable patients with DLBCL received prior NK cell therapy.

At the data cut off, the median duration of response for weight-based dosing cohorts and Part C was 225 days for patients with DLBCL and 171 days for patients with FL, with six patients continuing to respond to plamotamab monotherapy.

The poster will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

About Plamotamab

Plamotamab is an investigational tumor-targeted XmAb bispecific antibody that contains both a CD20 binding domain and a cytotoxic T-cell binding domain (CD3). CD20 is highly expressed across a range of B-cell tumors, including non-Hodgkin lymphoma (NHL). Engagement of CD3 by plamotamab activates T cells for highly potent and targeted killing of CD20-expressing tumor cells.

Plamotamab is currently being evaluated in a Phase 1 clinical study for the treatment of patients with CD20-expressing hematologic malignancies, including NHL. Preliminary safety and anti-tumor activity from the Phase 1 study indicates that plamotamab is generally well tolerated and demonstrates encouraging clinical activity as a monotherapy.

Xencor has entered an exclusive collaboration and worldwide license agreement with Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to develop and commercialize plamotamab and novel XmAb B-cell targeting bispecific antibodies that are designed to conditionally activate T cells through the CD28 co-stimulatory receptor.

On December 12, 2021 Seagen Inc. (Nasdaq:SGEN) reported promising efficacy and safety results from Part B of an open-label, phase 2 clinical trial evaluating ADCETRIS (brentuximab vedotin) in a novel combination with nivolumab, doxorubicin, and dacarbazine (AN+AD) as a frontline treatment for patients with advanced stage classical Hodgkin lymphoma (cHL) (Press release, Seagen, DEC 12, 2021, View Source [SID1234596831]). Data from this preliminary analysis were presented (Abstract #2454) as part of a poster presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta.

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The preliminary results demonstrated a complete response rate of 88 percent (95% CI: 75.9, 94.8) and overall response rate of 93 percent (95% CI: 82.7, 98.0) among 56 patients who had an end of treatment assessment on or prior to the data cutoff date. Patients received up to six cycles of treatment and were evaluated after two cycles of therapy and at the end of treatment. AN+AD was well-tolerated and no new safety signals were observed.

"I am excited about this combination of brentuximab vedotin and nivolumab along with a simplified chemotherapy regimen for the frontline treatment of patients with advanced stage classical Hodgkin lymphoma," said Hun Ju Lee, M.D., Associate Professor of Medicine, Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston. "This combination demonstrated a low incidence of peripheral neuropathy and the absence of febrile neutropenia. What we are learning from our research is that the use of two active targeted agents with distinct and complementary mechanisms of action in the first-line setting shows promising activity and a tolerable safety profile."

"We are optimistic about novel combination approaches to improve outcomes in patients following a diagnosis of classical Hodgkin lymphoma, and we are encouraged by these data evaluating ADCETRIS plus nivolumab, doxorubicin and dacarbazine as a first-line therapy," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "We look forward to complete results from this trial and adding to the breadth of evidence for ADCETRIS in the treatment of advanced classical Hodgkin lymphoma."

Efficacy:

Among 56 patients who had an end of treatment assessment on or prior to the data cutoff date, there was a complete response rate of 88 percent (95% CI: 75.9, 94.8) and overall response rate of 93 percent (95% CI: 82.7, 98.0).
Safety:

The most frequently reported treatment-related treatment-emergent adverse events (AEs) occurring in more than 20 percent of patients who received AN+AD included nausea (65%), fatigue (46%), peripheral sensory neuropathy (39%), alopecia (35%), diarrhea (30%) and constipation (25%).
Immune-mediated AEs were observed in 18 patients (32%) and eight patients (14%) experienced treatment-related treatment-emergent serious AEs.
Two patients (4%) experienced Grade > 3 peripheral neuropathy and no patients discontinued treatment due to peripheral neuropathy. No febrile neutropenia was observed, and there were no Grade 5 adverse events.
See ADCETRIS U.S. Important Safety Information, including Boxed Warning, below.

About the SGN35-027 Clinical Study

SGN35-027 is an ongoing open-label, multiple part, multicenter, phase 2 clinical trial evaluating two brentuximab vedotin treatment combinations in patients with advanced stage classical Hodgkin lymphoma. The trial includes three parts (Parts A, B, and C). Part A includes a combination of brentuximab vedotin and doxorubicin, vinblastine and dacarbazine (A+AVD), while Parts B and C include brentuximab vedotin in combination with nivolumab, doxorubicin, and dacarbazine (AN+AD). The primary endpoint for Part A is the proportion of patients with treatment-emergent incidence of rate of febrile neutropenia. The primary endpoint for Parts B and C is the proportion of participants with complete response at end of treatment, according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). Key secondary endpoints include safety, tolerability, ORR, and PFS. Incidence of adverse events is a secondary endpoint for Parts B and C.

About Classical Hodgkin Lymphoma

Classical Hodgkin lymphoma (cHL), Hodgkin disease, or Hodgkin, is a cancer of the blood. It starts when lymphocytes, a type of white blood cell, grow out of control. People with cHL have abnormal white blood cells called Reed-Sternberg cells in their lymph nodes. These cells usually have a special protein on their surface called CD30, which is a key marker of cHL. CD30 is present in approximately 95 percent of all cases of Hodgkin lymphoma. In 2021, it is estimated that there will be 8,830 new cases of Hodgkin lymphoma and an estimated 960 people will die of this disease in the U.S.1

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagen’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing cells.

ADCETRIS is indicated for the treatment of adult patients with:

previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine,
cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation,
cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates,
previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone,
sALCL after failure of at least one prior multi-agent chemotherapy regimen, and
primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.
ADCETRIS has received marketing authorization in more than 70 countries for certain types of relapsed or refractory Hodgkin lymphoma and sALCL.

Seagen and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) for injection U.S. Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

Contraindication

ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.
Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for bacterial, fungal, or viral infections.
Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid use in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
Most Common (≥20% in any study) Adverse Reactions

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug Interactions

Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations

Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.