Monjuvi (tafasitamab-cxix)

P1/2, N=4, Active, not recruiting, Pfizer | Trial primary completion date: May 2025 --> Aug 2024

P2, N=71, Active, not recruiting, The Lymphoma Academic Research Organisation | Recruiting --> Active, not recruiting

P2, N=25, Recruiting, Incyte Corporation | Initiation date: Jun 2024 --> Nov 2022

P1/2, N=4, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=70 --> 4 | Trial completion date: Feb 2029 --> May 2025 | Trial primary completion date: Feb 2027 --> May 2025

P1/2, N=70, Recruiting, Pfizer | Phase classification: P2 --> P1/2

P2, N=4, Terminated, Memorial Sloan Kettering Cancer Center | N=39 --> 4 | Trial completion date: Mar 2025 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Mar 2025 --> Aug 2024; Slow accrual rate

P1/2, N=47, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Jul 2024

P3, N=244, Recruiting, Beijing InnoCare Pharma Tech Co., Ltd.

P2/3, N=450, Completed, MorphoSys AG | Active, not recruiting --> Completed

P2, N=25, Recruiting, Incyte Corporation | Not yet recruiting --> Recruiting

Macrophages are one of the key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD19 antibody tafasitamab, approved in combination with lenalidomide for the treatment of relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL). Finally, combined treatment of tafasitamab and an anti-CD47 antibody resulted in enhanced tumor volume reduction and survival benefit in lymphoma xenograft mouse models. These findings provide evidence that CD47 blockade can enhance the phagocytic potential of tumor targeting immunotherapies such as tafasitamab and suggest there is value in exploring the combination in the clinic.

P2, N=25, Not yet recruiting, Incyte Corporation

P1/2, N=47, Not yet recruiting, M.D. Anderson Cancer Center

P1/2, N=27, Recruiting, Alvaro Alencar, MD | Not yet recruiting --> Recruiting

P2, N=41, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=53, Active, not recruiting, MorphoSys AG | Recruiting --> Active, not recruiting

P2, N=20, Not yet recruiting, University of Cologne | Trial completion date: Jul 2026 --> Apr 2027 | Trial primary completion date: May 2026 --> Feb 2027

P1/2, N=65, Recruiting, Incyte Biosciences Japan GK | Phase classification: P1 --> P1/2

The anti-CD19 monoclonal antibody tafasitamab, paired with the immunomodulator lenalidomide, mediates antibody-dependent cellular toxicity and cellular phagocytosis; the antibody-drug conjugate loncastuximab tesirine delivers the DNA-cross-linking agent tesirine via CD19 binding and internalization; and CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) products are engineered from autologous T cells. To date, clinical evidence on the effect of anti-CD19 therapy prior to CAR-T is restricted to small case series. Prospective studies and detailed analyses to understand how pre- and post-treatment CD19 expression correlates with clinical responses to subsequent CD19-directed therapy are needed to fully maximize treatment strategies.

The introduction of rituximab has improved the outcomes in CD20 positive cases. Other monoclonal antibodies, such as tafasitamab (anti-CD19), obinutuzumab (anti-CD20) and epratuzumab (anti-CD22) have been tested in trials (NCT05366218, NCT04920968, NCT00098839)...In contrast to ATP site inhibitors such as dasatinib and ponatinib, the novel first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor asciminib did not significantly impact ADCC in our settings. Our results suggest that asciminib should be considered in clinical trials.

P1, N=18, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=200, Recruiting, Incyte Biosciences Italy S.r.l

P3, N=654, Active, not recruiting, Incyte Corporation | Trial primary completion date: Aug 2024 --> Feb 2024

P1, N=65, Recruiting, Incyte Biosciences Japan GK | Phase classification: P1b/2 --> P1

P1, N=27, Recruiting, City of Hope Medical Center | Initiation date: Jan 2024 --> Jun 2024

P1, N=18, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=100, Recruiting, Academic and Community Cancer Research United | Not yet recruiting --> Recruiting

P1/2; Trial completion date: Apr 2023 --> Jun 2026 | Trial primary completion date: Apr 2023 --> Sep 2025

P1/2, N=54, Active, not recruiting, Incyte Corporation | Phase classification: P1b/2a --> P1/2 | Trial completion date: Oct 2023 --> Dec 2024 | Trial primary completion date: Oct 2023 --> Dec 2024

P2, N=70, Recruiting, Pfizer | Phase classification: P1b/2 --> P2

P=N/A, N=100, Recruiting, MorphoSys AG | N=1000 --> 100 | Trial completion date: Jul 2029 --> Aug 2026 | Trial primary completion date: Jul 2028 --> Oct 2025

P1, N=27, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2027 --> May 2028

We performed an SLR to understand the efficacy and real-world (RW) effectiveness of non–CAR T-cell therapies for R/R LBCL including tafasitamab with lenalidomide (tafa/len), polatuzumab with bendamustine/rituximab (pola-BR), loncastuximab, selinexor, epcoritamab, and glofitamab. Currently, the evidence base, particularly RW studies, for non–CAR T-cell R/R LBCL therapies is still limited. In comparison, 78 RW CAR T-cell therapy studies were published (Jacobson et al. Tandem Meeting.

Comparators were axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), loncastuximab tesirine (Lonca), polatuzumab vedotin + bendamustine + rituximab (Pola-BR), rituximab + gemcitabine + oxaliplatin (R-GemOx), tafasitamab + lenalidomide, and epcoritamab. Over 3 years, the estimated cumulative per-patient cost of glofitamab is projected to be the lowest when compared with per-patient costs of other available T-cell engaging therapies, resulting in cost savings after its formulary adoption for the treatment of R/R DLBCL after ≥2 lines of therapy.

A micro-costing analysis was developed to compare practice efficiency of treating patients with R/R DLBCL using epcoritamab versus comparator treatments (glofitamab, polatuzumab/bendamustine/rituximab [pola-BR], tafasitamab/lenalidomide [tafa-len], and axicabtagene ciloleucel [axi-cel]) over a time horizon of up to 1 year. Due to its unique SC administration, epcoritamab improves institutional practice efficiency despite more frequent dosing, saving personnel costs and inpatient costs. This could help to alleviate capacity constraints at infusion centers and ease patient scheduling. The resources saved (staff time, chair time, inpatient monitoring) can be redirected to other institutional needs, improving the availability and quality of healthcare services for patients.

Western blot analysis of splenocytes revealed that G1, 3, and 4 showed significantly lower expression of apoptosis-inducing protein gasdermin E on leukemic cells compared to G2, indicating reduced tumor pyroptosis in G2. In summary, application of the high affinity mAb tafasitamab prior to CART19 resulted in reduced CAR T apoptosis, diminished tumor cell pyroptosis, and reduction of CRS compared to lower affinity CD19 mAbs in preclinical models.

Participants must provide a baseline tumor tissue sample (fresh or archival), for biomarker analysis. Exclusion criteria include previous treatment with anti-CD47, anti-CD19 (other than CAR-T) or immunomodulatory agents, prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment, and participants with active, uncontrolled viral, bacterial or fungal infections.

Study statusThe in-progress non-interventional realMIND study is expected to end by approximately December 2025, or earlier, when: ≥50 patients treated with tafasitamab + LEN have been recruited into each of Group 1 and Group 2 with either prospective or retrospective data collection; and all prospectively-followed patients have ≥6 months follow-up after starting tafasitamab treatment, or have discontinued from the study for any reason, whichever occurs earlier. The results are anticipated to describe the real-world safety and effectiveness of tafasitamab for R/R DLBCL in US patients, with a focus on underrepresented racial and ethnic minorities, to help optimize outcomes of treatment and identify opportunities for further studies.

P1/2, N=51, Recruiting, MorphoSys AG | Phase classification: P1b/2 --> P1/2 | Trial completion date: Feb 2027 --> Oct 2027 | Trial primary completion date: May 2024 --> Nov 2024

Survivors of DLBCL have an increased risk of secondary primary malignancies; previous studies found that incidence of acute myeloid leukaemia (AML) nearly doubled in the post rituximab era...Due to severe chronic obstructive pulmonary disease, autologous transplant was excluded, thus request for Tafasitamablenalidomide under an extended access program was sent and approved in July 2022. After two cycles, lenalidomide was reduced because of grade 3-4 neutropenia poorly responsive to G-CSF...Patient started decitabine plus venetoclax protocol that is still ongoing...Patient has been candidated to allogenic transplant and azacitidine is now ongoing...Recently, the risk of SMN is also of particular concern in the CAR-T receivers. In conclusion a better comprehension of SPM/SMN pathology in DLBCL survivors is needed in order to guide the best “tailored” surveillance.

The current study highlights the importance of selecting appropriate CD19 detection tools and techniques for correct interpretation of CD19 expression. The findings presented herein can serve as a guideline to investigators and may help navigate treatment strategies in the clinical setting.