In this study, we further developed our protocol MCCS-Docker for protein-protein interactions and applied it to investigate the structural intricacies of CD3 interactions with therapeutic antibodies such as OKT3, UCHT1, Mosunetuzumab, Odronextumab, Glofitamab, and Epcoritamab using computational modeling techniques. Molecular dynamics simulations validated the stability of these interactions over time, confirming the reliability of the binding poses generated from docking studies. Overall, our study offered a novel method to predict critical residues in protein-protein interactions and enhanced the understanding of the structural determinants governing BsAb interactions with target proteins, offering valuable insights for designing and optimizing immunotherapeutic agents for NHL and related hematologic malignancies.

4 days ago

Journal

CD20 (Membrane Spanning 4-Domains A1)

Epkinly (epcoritamab-bysp) • Lunsumio (mosunetuzumab-axgb) • Columvi (glofitamab-gxbm)

Metabolic inhibition induces pyroptosis in uveal melanoma. (PubMed, Mol Cancer Res)

Although the bispecific tebentafusp is FDA-approved, immunotherapy has largely failed, likely given the poorly immunogenic nature of UM...In particular, the CPT1 inhibitor, etomoxir, induced propidium iodide uptake, caspase 3 cleavage and the release of HMGB1 and IL-1β, indicating that the observed cleavage of gasdermins led to pyroptosis...Together, these data show that metabolic inhibitors can induce pyroptosis in UM cell lines, potentially offering an approach to enhance inflammation-mediated immune targeting in metastatic UM patients. Implications: Induction of pyroptosis by metabolic inhibition may alter the tumor immune microenvironment and improve the efficacy of immunotherapy in uveal melanoma.

5 days ago

Journal • IO biomarker

CASP3 (Caspase 3) • HMGB1 (High Mobility Group Box 1) • IL1B (Interleukin 1, beta) • CPT1A (Carnitine Palmitoyltransferase 1A) • GSDME (Gasdermin E) • CASP1 (Caspase 1)

Kimmtrak (tebentafusp-tebn) • etomoxir (MIQ-001)

CO43805: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and/or CC-99282 in Participants With B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov)

P1, N=121, Recruiting, Hoffmann-La Roche | Trial completion date: Jul 2028 --> Mar 2029 | Trial primary completion date: Jul 2026 --> Mar 2027

6 days ago

Trial completion date • Trial primary completion date • Combination therapy

CD20 (Membrane Spanning 4-Domains A1)

CD20 expression

Gazyva (obinutuzumab) • Actemra IV (tocilizumab) • Lunsumio (mosunetuzumab-axgb) • iberdomide (CC-220) • Columvi (glofitamab-gxbm) • golcadomide (CC-99282)

Intrathecal Chemoprophylaxis to Prevent Neurotoxicity Associated With Blinatumomab Therapy for Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P2, N=20, Recruiting, Northside Hospital, Inc. | Trial completion date: Aug 2025 --> Dec 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

6 days ago

Trial completion date • Trial primary completion date • Adverse events

Blincyto (blinatumomab)

Clearing MRD positivity with blinatumomab in pediatric B-cell acute lymphoblastic leukemia: insights from droplet digital PCR and flow cytometry. (PubMed, Ann Hematol)

Starting from the initiation of blinatumomab treatment, with a median follow-up of 12 months, all patients remained in complete remission. Our study was the first to demonstrate that blinatumomab could further eradicate ddPCR MRD after patients achieve MFC-MRD undetectable status in B-ALL patients.

6 days ago

Journal • Minimal residual disease

ABL1 (ABL proto-oncogene 1)

Blincyto (blinatumomab)

A Study of CLN-978, a Subcutaneously Administered CD19-directed T Cell Engager, in Subjects With Systemic Lupus Erythematosus (clinicaltrials.gov)

P1, N=24, Recruiting, Cullinan Therapeutics Inc. | Not yet recruiting --> Recruiting

7 days ago

Enrollment open

CLN-978

EPCORE NHL-2: Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL) (clinicaltrials.gov)

P1/2, N=543, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting

8 days ago

Enrollment closed • Combination therapy

CD20 (Membrane Spanning 4-Domains A1)

CD20 positive

carboplatin • gemcitabine • Rituxan (rituximab) • lenalidomide • cytarabine • doxorubicin hydrochloride • cyclophosphamide • ifosfamide • oxaliplatin • etoposide IV • vincristine • prednisone • dexamethasone • bendamustine • Epkinly (epcoritamab-bysp)

A Study to Test How Well Different Doses of BI 764532 Are Tolerated by People With a Tumour in the Brain That is Positive for DLL3 (clinicaltrials.gov)

P1, N=20, Recruiting, Boehringer Ingelheim | N=35 --> 20 | Trial completion date: Aug 2026 --> Sep 2025 | Trial primary completion date: Aug 2026 --> Sep 2025

8 days ago

Enrollment change • Trial completion date • Trial primary completion date

DLL3 (Delta Like Canonical Notch Ligand 3)

DLL3 expression

obrixtamig (BI 764532)

Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 × CD3 bispecific antibody) in patients with recurrent ovarian cancer. (PubMed, Clin Transl Sci)

Integrating preclinical and clinical data determined a target trough concentration range of 5-30 mg/L, which supports evaluation of ubamatamab 250 mg with or without cemiplimab and 800 mg monotherapy once every 3 weeks in expansion cohorts. Preclinical data (cytokine release, tumor regression, monkey PK) had translational value in supporting regimen selection in dose escalation and subsequently in dose expansion after integration with patient data from dose escalation.

9 days ago

P1 data • Journal

MUC16 (Mucin 16, Cell Surface Associated)

MUC16 expression

Libtayo (cemiplimab-rwlc) • ubamatamab (REGN4018)

10d

DKTK_PMO_1605: The Bispecific PSMAxCD3 Antibody CC-1 in Patients with Castration Resistant Prostate Carcinoma (clinicaltrials.gov)

P1, N=86, Recruiting, University Hospital Tuebingen | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

10 days ago

Trial completion date • Trial primary completion date

CC-1

10d

Talisman: A Study to Evaluate Preventive Treatments for Talquetamab-related Oral Toxicity (clinicaltrials.gov)

P2, N=130, Recruiting, Janssen Research & Development, LLC | Active, not recruiting --> Recruiting

10 days ago

Enrollment open

Talvey (talquetamab-tgvs)

10d

IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301) (clinicaltrials.gov)

P3, N=680, Recruiting, Immunocore Ltd | Trial primary completion date: Dec 2026 --> Oct 2027

10 days ago

Trial primary completion date • Metastases

BRAF (B-raf proto-oncogene) • HLA-A (Major Histocompatibility Complex, Class I, A)

BRAF mutation • BRAF V600 • HLA-A*02

Opdualag (nivolumab/relatlimab-rmbw) • brenetafusp (IMC-F106C) • relatlimab (BMS-986016)

10d

Epcoritamab and Lenalidomide in Treating Patients With Refractory or Relapsed Immunodeficiency-Related Large B-Cell Lymphoma (clinicaltrials.gov)

P2, N=34, Not yet recruiting, Northwestern University

10 days ago

New P2 trial

lenalidomide • Epkinly (epcoritamab-bysp)

10d

Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors. (PubMed, Eur J Cancer)

Both treatment sequences are clinically feasible. A clinical benefit was noted in the sequential combination of ICIs followed by tebentafusp. This observation is limited by the retrospective nature of the study and merits further investigation in prospective clinical trials.

10 days ago

Journal • Checkpoint inhibition • IO biomarker • Metastases

GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11)

GNAQ mutation

Kimmtrak (tebentafusp-tebn)

11d

Minimal Residual Disease Measured after Treatment with Bispecifics in Relapsed Multiple Myeloma: Experience from an Academic Medical Center (ASH 2024)

Median number of prior lines was 4 (range 1-13), 19.4% had received CAR-T previously, and 12.9% had been previously exposed to another TCE.Twenty-three pts (74.2%) were enrolled in clinical trials (7 with teclistamab, Tec, 6 with talquetamab, Tal, and 10 with investigational agents). Twelve of these pts received TCE in combination with daratumumab and/or pomalidomide...MRD- seems to translate into long PFS, regardless of HR disease. Prospective studies on fixed duration treatment with TCE based on baseline risk and treatment response are needed.

11 days ago

IO biomarker • Minimal residual disease

clonoSEQ

Darzalex (daratumumab) • pomalidomide • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv)

11d

Use of CD19 CAR-T Cells in Adult B-Cell Acute Lymphoblastic Leukemia (B-ALL) with Minimal Residual Disease (MRD) Positivity at First Complete Remission: Preliminary Outcomes from a Phase I Clinical Trial (ASH 2024)

Incorporation of blinatumomab and/or inotuzumab in CR1 may mitigate the negative prognostic significance of MRD, however it is unclear if intensity of standard post-remission therapy can be safely reduced without compromising outcomes...We designed a phase I clinical trial to determine safety and tolerability of UCD19 CAR-T cell therapy for adults with B-ALL in MRD+ CR1 who are at high risk for relapse.Methods : Eligible patients include adults (≥18yo) with B-ALL in CR1 after induction therapy, with MRD positivity by either flow cytometry or NGS (Clonoseq)...Longer follow-up is needed to determine if remissions remain durable, and to determine the relationship between functional persistence (as measured by B-cell aplasia) and remission durability. Enrollment is ongoing at DL2.

11 days ago

Clinical • P1 data • CAR T-Cell Therapy • Minimal residual disease

IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8)

clonoSEQ

Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • UCD19 CAR T Cells

13d

A Clinical Study of TQB2029 for Injection in Subjects With Multiple Myeloma (clinicaltrials.gov)

P1, N=136, Recruiting, Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

13 days ago

Enrollment open

14d

MajesTEC-1: A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)

P2, N=194, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2025 --> Jun 2026

14 days ago

Trial completion date

Tecvayli (teclistamab-cqyv)

14d

BP42233: A Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of Forimtamig in Participants With Relapsed or Refractory Multiple Myeloma (r/r MM) (clinicaltrials.gov)

P1, N=225, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=480 --> 225 | Trial completion date: Aug 2026 --> Feb 2026 | Trial primary completion date: Aug 2026 --> Feb 2026

14 days ago

Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date

forimtamig (RG6234)

14d

A Study of JNJ-78278343, a T-Cell-Redirecting Agent Targeting Human Kallikrein 2 (KLK2), for Advanced Prostate Cancer (clinicaltrials.gov)

P1, N=260, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Nov 2024 --> Feb 2026

14 days ago

Trial primary completion date • Metastases

JNJ-8343

14d

ECOG-ACRIN E1910: Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P3, N=488, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Mar 2025

14 days ago

Trial completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • IGH (Immunoglobulin Heavy Locus) • ETV6 (ETS Variant Transcription Factor 6) • CD4 (CD4 Molecule) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1)

Rituxan (rituximab) • cytarabine • cyclophosphamide • etoposide IV • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • Truxima (rituximab-abbs) • mercaptopurine • Hemady (dexamethasone tablets) • Mabtas (rituximab biosimilar) • Starasid (cytarabine ocfosfate)

14d

A Study of JNJ-70218902 in Participants With Advanced Stage Solid Tumors (clinicaltrials.gov)

P1, N=82, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Dec 2024 --> Jun 2025

14 days ago

Trial primary completion date • Metastases

JNJ-8902

14d

RedirecTT-1: A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)

P1/2, N=228, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

14 days ago

Enrollment closed

Darzalex (daratumumab) • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv)

15d

GNC-035-103: A Study of GNC-035, a Tetra-specific Antibody, in Participants With Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)

P1, N=29, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Oct 2024 --> Jun 2025

15 days ago

Trial completion date • Trial primary completion date • Metastases

PD-L1 (Programmed death ligand 1)

nebratamig (GNC-035)

15d

TECTONIC: Study on the Clinical Efficacy of Teclistamab (clinicaltrials.gov)

P=N/A, N=100, Recruiting, Universitaire Ziekenhuizen KU Leuven | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> Dec 2024

15 days ago

Enrollment open • Trial initiation date

Tecvayli (teclistamab-cqyv)

15d

A Study of Runimotamab in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers (clinicaltrials.gov)

P1, N=123, Active, not recruiting, Genentech, Inc. | N=537 --> 123

15 days ago

Enrollment change • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2)

HER-2 positive • HER-2 expression

Herceptin (trastuzumab) • Actemra IV (tocilizumab) • runimotamab (RG6194)

15d

SWOG-S1318: Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia (clinicaltrials.gov)

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

15 days ago

Trial completion date

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CD4 (CD4 Molecule) • CSF1R (Colony stimulating factor 1 receptor)

ABL2 fusion

dasatinib • Blincyto (blinatumomab) • methotrexate • vincristine • mercaptopurine • Xatmep (methotrexate oral solution)

15d

EPCORE FL-1: Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Follicular Lymphoma (clinicaltrials.gov)

P3, N=500, Recruiting, Genmab | Trial completion date: Jun 2030 --> Oct 2030 | Trial primary completion date: Nov 2029 --> Oct 2030

15 days ago

Trial completion date • Trial primary completion date • Adverse events • Combination therapy

Rituxan (rituximab) • lenalidomide • Epkinly (epcoritamab-bysp)

15d

EPCORE DLBCL-2: A Study to Evaluate Change in Disease Activity of Subcutaneous (SC) Epcoritamab Combined With Intravenous and Oral Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) or R-CHOP in Adult Participants With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) (clinicaltrials.gov)

P3, N=900, Recruiting, Genmab | Trial primary completion date: Sep 2028 --> Jun 2027

15 days ago

Trial primary completion date • Combination therapy

ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6)

ALK positive

Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • prednisone • Epkinly (epcoritamab-bysp)

16d

EPCORE NHL-6: A Study to Evaluate Adverse Events of Subcutaneous (SC) Epcoritamab Administered in the Outpatient Setting in Adult Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Classic Follicular Lymphoma (clinicaltrials.gov)

P2, N=184, Recruiting, Genmab | Trial completion date: May 2029 --> Mar 2027 | Trial primary completion date: May 2029 --> Mar 2027

16 days ago

Trial completion date • Trial primary completion date • Adverse events

BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)

BCL6 translocation

Epkinly (epcoritamab-bysp)

16d

NP30179: A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov)

P1/2, N=860, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

16 days ago

Trial completion date • Trial primary completion date • Combination therapy

Gazyva (obinutuzumab) • Actemra IV (tocilizumab) • Columvi (glofitamab-gxbm)

16d

A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia (clinicaltrials.gov)

P1, N=137, Recruiting, Hoffmann-La Roche | Trial primary completion date: May 2027 --> Aug 2027

16 days ago

Trial primary completion date

Venclexta (venetoclax) • Actemra IV (tocilizumab) • Lunsumio (mosunetuzumab-axgb)

16d

EPCORE FL-2: Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Previously Untreated Follicular Lymphoma (clinicaltrials.gov)

P3, N=1080, Recruiting, Genmab | Trial completion date: May 2037 --> Nov 2037 | Trial primary completion date: May 2037 --> Nov 2037

16 days ago

Trial completion date • Trial primary completion date • Adverse events • Combination therapy

Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • Gazyva (obinutuzumab) • cyclophosphamide • vincristine • prednisone • bendamustine • Epkinly (epcoritamab-bysp)