plamotamab (XmAb13676) / Xencor - LARVOL DELTA

Upcoming Clinical Study Initiation Plans (Businesswire) - "Xencor plans to evaluate plamotamab in RA, in which patients have progressed through prior standard-of-care treatment and initiate a Phase 1b/2a proof-of-concept study in the first half of 2025. The Phase 1b portion of the study will select a priming and step-up dose regimen based on the regimen established in oncology and will assess the initial safety, efficacy, and biomarkers of plamotamab in patients with RA. The selected dose regimen will then be evaluated in the randomized Phase 2a portion, with efficacy determined at week 12."

New P1/2 trial • Rheumatoid Arthritis

Risk Factors for Severe Infection in Patients Receiving Bispecific Antibody Therapies for Lymphoma (ASH 2024) - "We evaluated characteristics of infection including time to infection, time from last treatment of bendamustine, autologous SCT, or CAR-T to infection, and outcomes after infection...17 R/R patients received BsAb as combination therapy with Polatuzumab-CHP (n=5), R-DHAOx (n=3), GemOx (n=3), lenalidomide (n=5), or RCHOP (n=1)...Patients were treated with epcoritamab (n=39), glofitamab (n=11), mosunetuzumab (n=16), and plamotamab (n=18)...Our study confirms that patients receiving BsAb have a high risk of severe infections, even in patients treated in the frontline setting or while on prophylaxis. Multivariate analysis showed no difference in risk of severe infection with regards to combination therapy, histology, product, or previous treatment and further research with larger cohorts is warranted to fully understand risk factors for infection in this high risk patient population."

Clinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Herpes Zoster • Infectious Disease • Lymphoma • Nephrology • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Richter's Syndrome • Varicella Zoster • CD20

Risk Factors for Cytokine Release Syndrome in Patients Receiving Bispecific Antibodies for B-Cell Lymphoma: A Single-Center, Retrospective Cohort Study (ASH 2024) - "Patients were treated with epcoritamab (Epco) (n=39, 46.4%), glofitamab (Glofit) (n=11, 13.1%), plamotamab (Plamo) (n=18, 21.4%) and mosunetuzumab (Mosun) (n=16, 19.1%)...CRS was managed with additional steroids in 14 patients (29.2%) and tocilizumab in 15 patients (31.3%)...Inflammatory marker levels, prior CAR-T, and prior bendamustine did not impact the risk of CRS. Further studies in larger data sets are needed to identify patients of high CRS risk to allow for early management, and of low risk to allow for treatment in the outpatient setting."

Cytokine release syndrome • IO biomarker • Retrospective data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diabetes • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • CRP

Plamotamab: First Presentation of Subcutaneous Administration in a Phase 1 Dose Escalation Study in Heavily Pretreated R/R NHL Patients Who Had Prior CAR-T Cell Therapy (ASH 2024) - P1 | "SC dosing had favorable PK with Cmax lower than IV administration, with lower incidence and severity of CRS after the 1st step-up dose. Plamotamab is an active and tolerable drug for further development in CD20+ disease."

CAR T-Cell Therapy • Clinical • P1 data • Acute Respiratory Distress Syndrome • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Congestive Heart Failure • Diffuse Large B Cell Lymphoma • Fatigue • Heart Failure • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • CD20

XmAb13676-01: Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies (clinicaltrials.gov) - P1 | N=154 | Completed | Sponsor: Xencor, Inc. | Active, not recruiting ➔ Completed | N=270 ➔ 154 | Trial completion date: Jan 2025 ➔ Apr 2024 | Trial primary completion date: Oct 2024 ➔ Apr 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Xencor Reports Third Quarter 2024 Financial Results (Businesswire) - "Internal Clinical-Stage Program Updates:...Plamotamab (CD20 x CD3): Xencor previously completed a Phase 1 clinical study of plamotamab in hematologic cancers. Data from subcutaneous dosing cohorts in patients with relapsed or refractory non-Hodgkin’s lymphoma will be presented at the 66th American Society of Hematology Annual Meeting in a poster titled 'First Presentation of Subcutaneous Administration in a Phase 1 Dose Escalation Study in Heavily Pretreated R/R NHL Patients Who Had Prior CAR-T Cell Therapy'."

P1 data • Non-Hodgkin’s Lymphoma

Safety and Efficacy of Bispecific Antibodies in Adults with Large B-Cell Lymphomas: A Systematic Review of Clinical Trial Data. (PubMed, Int J Mol Sci) - "BsAbs appear to have superior tolerability, but inferior efficacy to CAR T-cell therapies in adults with LBCL. Future research on safety and efficacy should focus on evaluating adverse event timing and management, the impact on the patient's quality of life, the burden on the healthcare system, and overall survival outcomes."

Journal • Review • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

Xencor Regains CD20 x CD3 Bispecific T-Cell Engager (Businesswire) - "Xencor, Inc...announced it will regain exclusive worldwide rights to plamotamab, a CD20 x CD3 bispecific T-cell engager, which Xencor advanced through Phase 1 clinical development in hematologic cancers. In 2021, Xencor entered a collaboration and license agreement with Janssen Biotech, Inc. to develop and commercialize plamotamab and novel B-cell targeting bispecific antibodies designed to conditionally activate T cells through the CD28 co-stimulatory receptor....Xencor has been notified that Janssen will terminate its rights to plamotamab under the collaboration and license agreement. Janssen has retained its rights to develop and commercialize B-cell targeting CD28 bispecific antibodies, including JNJ-9401 (PSMA x CD28) and JNJ-1493 (CD20 x CD28)."

Licensing / partnership • Hematological Malignancies • Leukemia • Lymphoma • Metastatic Castration-Resistant Prostate Cancer • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

XmAb13676-01: Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies (clinicaltrials.gov) - P1 | N=270 | Active, not recruiting | Sponsor: Xencor, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

SAFETY AND EFFICACY OF ANTICD20-CD3 BISPECIFIC T-CELL ENGAGING ANTIBODIES IN THE MANAGEMENT OF RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A SYSTEMATIC REVIEW OF CLINICAL TRIALS (EHA 2023) - "In the trials, mosunetuzumab, glofitamab, epcoritamab, odronextamab, IGM-2323, and plamotamab were identified as antiCD20-CD3 bsAbs, which are evaluated against RRDLBCL as monotherapy and in combination regimens (Table). Based on our analysis , antiCD20-CD3 bsAbs are safe and efficacious. Among these drugs, glofitamab, epcoritamab and odronextamab as monotherapy and/or in combination regimens are the most effective therapies against RRDLBCL. Drug (s) **Author Efficac y ORR, CR per Lugano/RR C for ML criteria **CRS Overall/G 3 per ASTCT/ Lee et al criteria Overall Toxicity G≥3 per CTCAE CNS Toxicity G≥3 Per CTCAE aNHL 35%Mosun IV Budde et al."

Clinical • Review • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The evolving therapy of DLBCL: Bispecific antibodies (ICML 2023) - "In a small, randomised phase 2 study, complete response (CR) was seen in 40% of patients in PV-BR group, compared to 17% of patients in the BR group, leading to what appeared to be a PFS plateau around 30% at 2 years for the novel combination.6 L-MIND, a phase 2 study of the combination of the anti-CD19 antibody tafasitamab and lenalidomide showed a similar CR rate of 40% in r/r DLBCL patients, and these responses were highly durable.7 Even though this study seems to have included an unusually good-risk patient group, the combination of tafasitamab and lenalidomide has been approved for r/r DLBCL in the United States ad the European Union, as well as the combination of PV and BR. Other novel agents have also been approved based on data from phase 2 studies; the selective nuclear export inhibitor Selinexor and the anti-CD19 ADC loncastuximab tesirine, which led to CR in 12% and 24% of patients, respectively.8, 9 Despite these considerable improvements, the most..."

IO biomarker • Diffuse Large B Cell Lymphoma • Oncology • CD22 • CD79B • CD8 • FCGR3A • PD-1

[VIRTUAL] Approaches to Therapy of Richter Syndrome (SOHO 2021) - P2 | "Hematologic toxicity was reported in 65% of patients, with infections as most common severe non-hematologic toxicity in 28% of patients.29 The reported ORR in a retrospective series of 48 patients with DLBCL-RT is 37%, with a median OS of 35 months.30 The anti-CD20 ofatumumab (O) was also combined with CHOP showing an ORR of 46% (CR 27%, PR 19%) with a median PFS of 6 months and a median OS of 11 months. As for R-CHOP, infections and hematologic toxicities (thrombocytopenia, febrile neutropenia, sepsis) were the main adverse events.31,32 Due to its indication in MYC rearranged de novo DLBCL, R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) was investigated in RTDLBCL showing an ORR of 20%, a median PFS of 3 months and a median OS of 6 months, with worse PFS and OS in patients with underlying deletion 17p and complex karyotype. Febrile neutropenia and infections were reported as main toxicities.33 Response rates of ~40% with..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hodgkin Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • CDKN2A • CSF2 • FDG PET • NOTCH1 • PLCG2 • TP53

Phase 2 Study of Plamotamab Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in R/R DLBCL (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: Xencor, Inc. | N=240 ➔ 3 | Trial completion date: Jun 2031 ➔ Feb 2023 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2027 ➔ Dec 2022; The study has been terminated early by the sponsor due to business decision.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Phase 2 Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Plamotamab Combined with Tafasitamab (Tafa) + Lenalidomide (Len) Vs Tafa+Len in Relapsed or Refractory DLBCL (ASH 2022) - P2 | "Objective response, overall survival, and duration of response are secondary endpoints. Subjects continue study treatment until progression and are followed for long-term survival.Summary: The XmAb13676-03 trial has started enrollment and is registered at Clinicaltrials.gov (NCT05328102) and EudraCT (2021-003658-22) and anticipates opening centers in the US, EU, and Asia."

Clinical • P2 data • Anemia • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase 1 Study of Plamotamab, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin's Lymphoma: Recommended Dose Safety/Efficacy Update and Escalation Exposure-Response Analysis (ASH 2022) - P1 | "Plamotamab demonstrated evidence of clinical activity in heavily pretreated pts with DLBCL and FL with promising responses in pts with prior CAR-T therapy. CRS was generally manageable with premedication. Safety and efficacy evaluation of pts at the RD is currently ongoing, and updated results will be provided."

Clinical • P1 data • Anemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock • Thrombocytopenia • CD20 • IL6

Plamotamab: Expiry of patents in US/ex-US in 2035 (Xencor) - Annual Report 2022

Patent • Hematological Malignancies • Oncology

XmAb13676-01: Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies (clinicaltrials.gov) - P1 | N=270 | Recruiting | Sponsor: Xencor, Inc. | N=160 ➔ 270 | Trial completion date: Oct 2025 ➔ Jan 2025 | Trial primary completion date: Jul 2023 ➔ Oct 2024

Enrollment change • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Xencor Highlights 2023 Corporate Priorities and Provides Portfolio Updates (Businesswire) - "Plamotamab: Xencor plans to...Continue enrolling patients into the Phase 1 subcutaneous dose escalation study; Vudalima: Xencor plans to...Continue enrolling patients into the two Phase 2 clinical studies of vudalimab; XmAb104: Xencor plans to: Continue enrolling patients into the expansion portion of the Phase 1 clinical study; XmAb819: . Xencor plans to...Continue enrolling patients into the Phase 1 dose-escalation study in patients with RCC."

Enrollment status • Genito-urinary Cancer • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

Xencor Presents Data from Phase 1 Study of Plamotamab in Relapsed or Refractory Non-Hodgkin Lymphoma at the American Society of Hematology Annual Meeting (Businesswire) - P1 | N=160 | NCT02924402 | Sponsor: Xencor, Inc | "Xencor, Inc...today announced additional clinical data from expansion cohorts in its Phase 1 study of plamotamab, a CD20 x CD3 bispecific antibody, in patients with relapsed or refractory non-Hodgkin lymphomas....The safety profile of plamotamab was consistent with previous results....In the efficacy evaluable population of patients with FL, the ORR was 87.5% (7/8), and the CR rate was 50.0% (4/8). In the ITT population, the ORR was 80.0% (8/10), and the CR rate was 40.0% (4/10). The mDOR for both populations had not been reached."

P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PHASE 2 RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PLAMOTAMAB COMBINED WITH TAFASITAMAB (TAFA) + LENALIDOMIDE (LEN) VS TAFA+LEN IN RELAPSED OR REFRACTORY DLBCL (EHA 2022) - "Subjects continue study treatment until progr ession and are followed for long - term survival . Conclusion The XmAb13676-03 trial is registered at EudraCT (2021- 003658-22 ) and anticipates enrolling in centers in the US, EU , and Asia ."

Clinical • P2 data • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Xencor to Present New Clinical Data from the Phase 1 Study of Plamotamab in Relapsed or Refractory Non-Hodgkin’s Lymphoma at the American Society of Hematology Annual Meeting (Businesswire) - P1 | N=160 | NCT02924402 | Sponsor: Xencor, Inc | "Xencor, Inc...announced that clinical data from expansion cohorts in its Phase 1 study of plamotamab, a CD20 x CD3 bispecific antibody, in patients with relapsed or refractory non-Hodgkin’s lymphoma will be presented in a poster session during the 64th American Society of Hematology (ASH) Annual Meeting in New Orleans, Louisiana on Monday, December 12, 2022...The safety analysis included all 36 patients. The most common adverse event (AE) was cytokine release syndrome (CRS), which occurred in 72.2% of patients, with no patients experiencing Grade 3 or 4 CRS. Grade 3 AEs affecting greater than 10% of patients included anemia (19.4%), neutropenia (16.7%), neutrophil count decrease (16.7%) and thrombocytopenia (11.1%)."

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Safety and Anti-Tumor Activity of Plamotamab (XmAb13676), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Subjects with Relapsed/Refractory Non-Hodgkin’s Lymphoma (ASH 2021) - P1 | "Cytokine release syndrome (CRS) prophylaxis with dexamethasone, antihistamine, and acetaminophen was mandated prior to each administration of plamotamab. Plamotamab demonstrated evidence of clinical activity in heavily pretreated subjects with R/R NHL. CRS was generally manageable with premedication. The study is ongoing with further optimization of dose and schedule."

Clinical • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Inflammation • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CD20

Study to Evaluate Safety and Tolerability of XmAb13676 in Patients With CD20-expressing Hematologic Malignancies (clinicaltrials.gov) - P1; N=160; Recruiting; Sponsor: Xencor, Inc.; Trial primary completion date: Aug 2021 ➔ Jul 2023

Clinical • Trial primary completion date • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Management of Bispecific Toxicity: Cytokine Release Syndrome (CRS) in Non-Hodgkins Lymphoma for the Advanced Practice Provider (APP) (PPLC 2022) - "RESULTS A total of 10 articles were identified matching our search criteria Mosentuzumab, Glofitamab, Plamotamab, Odronnextamab, and Epcoritamab are the latest bispecific antibodies with published data for the treatment of relapsed refractory NHL. We created a broad overview of these new therapies, their MOAs, response rates, risk of CRS associated with each drug, CRS median onset and durations, identifying infusion reaction versus CRS, as well as CRS management strategies. CONCLUSION By creating a comprehensive review of the published data on bispecific antibodies in development for relapsed refractory NHL setting, APPs will be able to rapidly identify CRS, and have increased knowledge in the new strategies available for management of CRS, improving patient safety and toxicity outcomes."

Cytokine release syndrome • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 2 Study of Plamotamab Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in R/R DLBCL (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Xencor, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19