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6d
BRAVO: Brain Stem Gliomas Treated With Adoptive Cellular Therapy During Focal Radiotherapy Recovery Alone or With Dose-intensified Temozolomide (Phase I) (clinicaltrials.gov)
P1, N=21, Active, not recruiting, University of Florida | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
Trial completion date • Trial primary completion date
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temozolomide • cyclophosphamide • fludarabine IV
11d
Phase classification
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Keytruda (pembrolizumab) • Tab-cel (tabelecleucel)
19d
Escalating Doses of AZD0486, a Novel CD19xCD3 T-Cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma (ASH 2024)
Median prior lines of therapy was 3 (range 2–12), 18 (38%) pts received prior lenalidomide–based therapy, 7 (15%) pts received prior chimeric antigen receptor T-cell therapy (CAR-T), and 4 (9%) received prior CD20 TCE therapy. AZD0486 offers high response rates in pts with R/R FL at target doses ≥2.4 mg. Responses were durable. 2SUD allows safe administration of the target dose up to at least 15 mg.
Clinical • Minimal residual disease
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CD20 negative
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Foresight CLARITY™
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lenalidomide • AZD0486
21d
Vδ2 T-cell engagers bivalent for Vδ2-TCR binding provide anti-tumor immunity and support robust Vγ9Vδ2 T-cell expansion. (PubMed, Front Oncol)
Bispecific engagers that incorporated the bivalent Vδ2-TCR specific VHH as well as a tumor antigen specific VHH triggered antitumor effector functions and supported expansion of Vγ9Vδ2 T-cells in vitro and in an in vivo model in NOG-hIL-15 mice. By enhancing the number of Vγ9Vδ2 T-cells available to exert antitumor effector functions, these novel Vδ2-bivalent bispecific T cell engagers may promote the overall efficacy of bispecific Vγ9Vδ2 T-cell engagement, particularly in patients with relatively low levels of Vγ9Vδ2 T-cells.
Journal
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PD-1 (Programmed cell death 1)
21d
Nanoradiosentizers with X ray-actuatable supramolecular aptamer building units for programmable immunostimulatory T cell engagement. (PubMed, Biomaterials)
The CA-mediated post-IR tumor-T cell engagement could override the immunosuppressive barriers in TME and enhance T cell-mediated recognition and elimination of tumor cells while minimizing systemic toxicities. Overall, this work offers an innovative approach to enhance the radio-immunotherapeutic efficacy in the clinics.
Journal
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
28d
INTACT: Study of the Efficacy of Intratumoral L19IL2 or L19TNF or L19IL2/L19TNF, in Combination with Pembrolizumab, in Unresectable Melanoma Patients (clinicaltrials.gov)
P2, N=162, Recruiting, Philogen S.p.A. | Active, not recruiting --> Recruiting | Initiation date: Dec 2023 --> Jul 2024
Enrollment open • Trial initiation date • Combination therapy • Checkpoint inhibition
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Keytruda (pembrolizumab) • Nidlegy (darleukin/fibromun)
28d
New P1 trial • Combination therapy
|
JNJ-8543 • rezetamig (JNJ-8780)
1m
A Study of OnCARlytics (CF33-CD19) in Combination with Blinatumomab in Adults with Advanced or Metastatic Solid Tumors (OASIS) (clinicaltrials.gov)
P1, N=33, Recruiting, Imugene Limited | N=52 --> 33 | Trial completion date: Sep 2025 --> May 2029 | Trial primary completion date: Sep 2024 --> Jun 2027
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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Blincyto (blinatumomab) • VAXinia (CF33-hNIS) • onCARlytics (CF33-CD19)
1m
SHR-7787-101: A Trial of SHR-7787 Injection in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=201, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting
Enrollment open • Metastases
1m
Trial initiation date • Checkpoint inhibition • Checkpoint block
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Keytruda (pembrolizumab)
1m
CD200R1 immune checkpoint blockade by the first-in-human anti-CD200R1 antibody 23ME-00610: molecular mechanism and engineering of a surrogate antibody. (PubMed, MAbs)
This engineering approach does not require a priori knowledge of structural and functional mapping of antibody-antigen interaction and thus is generally applicable for therapeutic antibody development when desired ortholog binding is lacking. These findings provide foundational insights as 23ME-00610 advances in clinical studies to gain understanding of the hCD200R1 immune checkpoint as a target in immuno-oncology.
P1 data • Journal • Checkpoint inhibition • IO biomarker • Checkpoint block
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CD200 (CD200 Molecule) • CD200R1 (CD200 Receptor 1)
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23ME-00610
1m
SAIL66, a next generation CLDN6-targeting T-cell engager, demonstrates potent antitumor efficacy through dual binding to CD3/CD137. (PubMed, J Immunother Cancer)
Our data demonstrate that SAIL66, designed to engage CLDN6, CD3, and CD137, has the potential to enhance antitumor activity and provide a potent therapeutic option for patients with ovarian and other solid tumors expressing CLDN6. Clinical trials are currently underway to evaluate the safety and efficacy of SAIL66.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CLDN6 (Claudin 6) • CD4 (CD4 Molecule) • TNFRSF9 (TNF Receptor Superfamily Member 9)
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CLDN6 expression • CLDN6 positive
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SAIL66
1m
The landscape of T-cell engagers for the treatment of follicular lymphoma. (PubMed, Oncoimmunology)
CD3 × CD20 BsAbs have shown the most promise in clinical development for B-NHL patients, with structural variations affecting their target affinity and potency. This review summarizes the current clinical trials of BsAbs for relapsed/refractory FL, highlighting the approval of some agents, their role in first-line treatment or combination therapies, their toxicity profiles, and the future of this therapeutic approach compared to other immune cell therapies.
Review • Journal
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CD20 (Membrane Spanning 4-Domains A1)
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Epkinly (epcoritamab-bysp) • Lunsumio (mosunetuzumab-axgb) • Columvi (glofitamab-gxbm) • Ordspono (odronextamab)
2ms
Trial primary completion date • Post-transplantation
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Rituxan (rituximab) • Tab-cel (tabelecleucel)
2ms
Peripheral blood and tumor gene expression as biomarkers and potential predictors of clinical outcome with HST-1011, an oral CBL-B inhibitor (SITC 2024)
Conclusions HST-1011 was associated with dose-dependent changes in peripheral blood pharmacodynamic measures that were sustained with repeated dosing and pre-treatment tumor WTS provided preliminary suggestion of a potential enrichment approach for a study population most likely to benefit from HST-1011. Monotherapy dose-optimization and combination with anti-PD-1 are ongoing.
Clinical • Clinical data • PD(L)-1 Biomarker • IO biomarker
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Xerna TME™ Panel
2ms
SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2. (PubMed, Front Immunol)
Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB-dependent transcription of CRS-related inflammatory cytokines. Targeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.
Journal • IO biomarker
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IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • TLR4 (Toll Like Receptor 4) • CD40 (CD40 Molecule) • IL1B (Interleukin 1, beta)
2ms
New trial
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Immuncell-LC (GCC4002)
2ms
New P1 trial
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STMN2 (Stathmin 2)
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SCG101
2ms
A B7-H3-targeted CD28 bispecific antibody enhances the activity of anti-PD1 and CD3 T-cell engager immunotherapies. (PubMed, Mol Cancer Ther)
XmAb808 as monotherapy and in combination with an anti-PD1 antibody is currently in clinical development in patients with advanced solid tumors. Our results suggest that XmAb808 may also combine with tumor antigen-targeted anti-CD3 (Signal 1) T-cell engagers.
Journal • PD(L)-1 Biomarker • IO biomarker
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IFNG (Interferon, gamma) • CD276 (CD276 Molecule) • BCL2L1 (BCL2-like 1) • IL2RA (Interleukin 2 receptor, alpha) • IL2 (Interleukin 2) • CD28 (CD28 Molecule)
2ms
Neoadjuvant L19IL2/L19TNF- Pivotal Study (clinicaltrials.gov)
P3, N=214, Active, not recruiting, Philogen S.p.A. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2028
Enrollment closed • Trial completion date • Surgery
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BRAF (B-raf proto-oncogene)
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Nidlegy (darleukin/fibromun)
2ms
A Trial of SHR-7787 Injection in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=201, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.
New P1/2 trial • Metastases
3ms
MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers. (PubMed, J Immunother Cancer)
Humanized MHC-dKO immunodeficient mice allow and refine the preclinical testing of immunotherapy agents for which experimentation is precluded in conventional immunodeficient mice due to severe xGVHD.
Preclinical • Journal • Checkpoint inhibition
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • TNFRSF9 (TNF Receptor Superfamily Member 9)
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Opdivo (nivolumab) • Yervoy (ipilimumab) • cyclophosphamide
3ms
CD4+ tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts. (PubMed, Oncoimmunology)
A promising approach based on the production of bispecific T cell-engagers (TCE) by engineered T cells (STAb-T therapy) improves the efficacy of current T cell redirection strategies against tumor-associated antigens in hematological tumors...We confirmed that the standard TIL expansion protocol promotes the loss of tumor-dominant T cell clones and the overgrowth of virus-reactive TCR clonotypes that were marginally detectable in primary tumors. We demonstrated the antitumor activity of TILSTAb both in vitro and in vivo when administered intratumorally and systemically in an autologous immune-humanized PDX EGFR+ NSCLC mouse model, where tumor regression was mediated by TCE-redirected CD4+ TIL bearing non-tumor dominant clonotypes.
Journal • Tumor-infiltrating lymphocyte
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EGFR (Epidermal growth factor receptor) • CD4 (CD4 Molecule) • TRB (T Cell Receptor Beta Locus)
3ms
A novel bispecific T-cell engager using the ligand-target csGRP78 against acute myeloid leukemia. (PubMed, Cell Mol Life Sci)
In a xenograft mouse model of AML, treatment with GRP78-CD3/BiTE prolonged the survival time of the mice. Our findings demonstrate that GRP78-CD3/BiTE is effective and selective for eliminating csGRP78-expressing AML cells and suggest that this approach to targeted immunotherapy could lead to effective new treatments for AML.
Journal
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
3ms
Complementary dual-virus strategy drives synthetic target and cognate T-cell engager expression for endogenous-antigen agnostic immunotherapy. (PubMed, Nat Commun)
VSVΔ51-mediated HER2T expression simulates HER2-positive status in tumours, enabling effective treatment with the antibody-drug conjugate trastuzumab emtansine in vitro, ex vivo, and in vivo...This dual-virus therapeutic strategy demonstrates potent curative efficacy in vivo in female mice using CD3+ infiltrate for anti-tumour immunity. Our findings showcase the ability to tailor the tumour microenvironment using oncolytic viruses, thereby enhancing compatibility with "off-the-shelf" targeted therapies.
Journal • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2)
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Kadcyla (ado-trastuzumab emtansine)
3ms
Trial completion date
|
HER-2 (Human epidermal growth factor receptor 2)
|
nCounter® PanCancer Immune Profiling Panel
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cyclophosphamide • citoplurikin (IRX-2) • omeprazole
3ms
A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic NSCLC. (PubMed, JTO Clin Res Rep)
Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.
P1 data • Journal • Combination therapy • Metastases
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CD27 (CD27 Molecule)
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Tecentriq (atezolizumab) • varlilumab (CDX 1127)
4ms
SHR-9539-101: A Clinical Study of SHR-9539 in Patients With Multiple Myeloma (clinicaltrials.gov)
P1, N=138, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting
Enrollment open
4ms
New P1 trial • Checkpoint inhibition • Checkpoint block
|
Keytruda (pembrolizumab)
4ms
Trial primary completion date • Trispecific
|
BCL2 (B-cell CLL/lymphoma 2)
|
JNJ-8543
4ms
New P1 trial
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
5ms
Engineering a tumor-selective prodrug T-cell engager bispecific antibody for safer immunotherapy. (PubMed, MAbs)
Furthermore, we demonstrate that a similar masking strategy can be used to create a pro-drug form of the frequently used anti-CD3 antibody SP34. This study showcases an approach to developing immune-modulating therapeutics that prioritizes safety and has the potential to advance cancer immunotherapy treatment strategies.
Journal
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MMP2 (Matrix metallopeptidase 2)
5ms
SHR-9539-101: A Clinical Study of SHR-9539 in Patients With Multiple Myeloma (clinicaltrials.gov)
P1, N=138, Not yet recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd.
New P1 trial
5ms
Activated Autologous T Cells Against Glioma Cancer Stem Cell Antigens for Patients With Recurrent Glioblastoma (clinicaltrials.gov)
P1, N=10, Not yet recruiting, Jeremy Rudnick, M.D | Trial completion date: Jun 2025 --> Dec 2026 | Trial primary completion date: Jun 2023 --> Dec 2025
Trial completion date • Trial primary completion date
|
KROS-201
5ms
New P1/2 trial • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1) • PD-L2 (Programmed Cell Death 1 Ligand 2) • PRAME (Preferentially Expressed Antigen In Melanoma)
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Tevimbra (tislelizumab-jsgr) • cyclophosphamide • Bria-OTS
5ms
NeoIRX: Pembrolizumab, IRX-2, and Chemotherapy in Triple Negative Breast Cancer (clinicaltrials.gov)
P2, N=12, Active, not recruiting, Providence Health & Services | Trial primary completion date: Jun 2024 --> Jul 2023
Trial primary completion date
|
Keytruda (pembrolizumab) • doxorubicin hydrochloride • cyclophosphamide • citoplurikin (IRX-2)
5ms
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG) (clinicaltrials.gov)
P1, N=14, Terminated, Nicholas Butowski | Active, not recruiting --> Terminated; Industry sponsor decision
Trial termination
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
varlilumab (CDX 1127) • Hiltonol (poly-ICLC) • IMA950
6ms
TACTIC-2: TAC T-cells for the Treatment of HER2-positive Solid Tumors (clinicaltrials.gov)
P1/2, N=30, Terminated, Triumvira Immunologics, Inc. | N=110 --> 30 | Trial completion date: Jun 2027 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Dec 2023; Study terminated by Sponsor for commercial reasons
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • BRCA (Breast cancer early onset)
|
Keytruda (pembrolizumab) • cyclophosphamide • TAC100-HER2
6ms
Study of ADXS-503 With or Without Pembro in Subjects With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=24, Completed, Advaxis, Inc. | Recruiting --> Completed | N=74 --> 24
Trial completion • Enrollment change • Combination therapy • Metastases
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
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Keytruda (pembrolizumab) • ADXS-503
6ms
Genetically redirected HBV-specific T cells target HBsAg-positive hepatocytes and primary lesions in HBV-associated HCC. (PubMed, Clin Mol Hepatol)
Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient's blood. SCG101 T-cell therapy showed encouraging efficacy and safety in pre-clinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.
Journal
|
STMN2 (Stathmin 2)
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SCG101
6ms
A Phase 1/2a Study of 23ME-00610 in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
P1/2, N=141, Active, not recruiting, 23andMe, Inc. | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Mar 2025
Trial completion date • Trial primary completion date
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23ME-00610