^
    2ms
    Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
    P2, N=32, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Aug 2024
    Trial completion • Trial completion date • Metastases
    |
    CEACAM5 (CEA Cell Adhesion Molecule 5) • CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
    3ms
    T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine M9241 in Localized High- and Intermediate-Risk Prostate Cancer Treated With Androgen Deprivation Therapy (clinicaltrials.gov)
    P2, N=65, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Aug 2026
    Trial completion date • Trial primary completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    PDS01ADC
    3ms
    T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine M9241 in Localized High- and Intermediate-Risk Prostate Cancer Treated With Androgen Deprivation Therapy (clinicaltrials.gov)
    P2, N=65, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Aug 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    PDS01ADC
    4ms
    A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov)
    P1/2, N=107, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    Jingzhuda (entinostat) • bintrafusp alfa (M7824) • PDS01ADC
    5ms
    20-C-0012: Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov)
    P1, N=100, Recruiting, National Cancer Institute (NCI) | N=66 --> 100
    Enrollment change • Combination therapy • Metastases
    |
    CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • PDS01ADC
    7ms
    Enzalutamide and M9241 in PET Positive Recurrent Prostate Cancer (pprPC) Without Testosterone Lowering Therapy (clinicaltrials.gov)
    P2, N=55, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Xtandi (enzalutamide capsule) • PDS01ADC
    7ms
    A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov)
    P1/2, N=107, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025
    Trial completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    Jingzhuda (entinostat) • bintrafusp alfa (M7824) • PDS01ADC
    10ms
    Preclinical and clinical studies of a tumor targeting IL-12 immunocytokine. (PubMed, Front Oncol)
    NHS-IL12 is currently being evaluated clinically in combination with various therapeutic modalities, including chemotherapy, radiation therapy, immune checkpoint inhibition, vaccines, and epigenetic modulation. Here we review the preclinical and clinical studies involving NHS-IL12 for the treatment of solid malignancies.
    Preclinical • Journal
    |
    CD8 (cluster of differentiation 8)
    |
    PDS01ADC
    10ms
    21-C-0001: M9241 in Combination With Docetaxel in Adults With Metastatic Castration Sensitive and Castration Resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=86, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    docetaxel • abiraterone acetate • prednisone • bintrafusp alfa (M7824) • PDS01ADC
    11ms
    20-C-0012: Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov)
    P1, N=66, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    bintrafusp alfa (M7824) • PDS01ADC
    1year
    Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
    P2, N=32, Active, not recruiting, National Cancer Institute (NCI) | Completed --> Active, not recruiting | N=23 --> 32 | Trial completion date: Feb 2023 --> Jan 2026
    Enrollment closed • Enrollment change • Trial completion date • Metastases
    |
    CEACAM5 (CEA Cell Adhesion Molecule 5) • CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
    1year
    Enzalutamide and M9241 in PET Positive Recurrent Prostate Cancer (pprPC) Without Testosterone Lowering Therapy (clinicaltrials.gov)
    P2, N=55, Not yet recruiting, National Cancer Institute (NCI)
    New P2 trial
    |
    CD4 (CD4 Molecule)
    |
    Xtandi (enzalutamide capsule) • PDS01ADC
    1year
    NHS-IL12 Monotherapy and in Combination With M7824 in Advanced Kaposi Sarcoma (clinicaltrials.gov)
    P1/2, N=64, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2028
    Trial completion date • Combination therapy • Metastases
    |
    CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • PDS01ADC
    1year
    20-C-0012: Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov)
    P1, N=66, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Sep 2023 --> Dec 2023
    Trial primary completion date • Combination therapy • Metastases
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    bintrafusp alfa (M7824) • PDS01ADC
    over1year
    Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov)
    P1/2, N=51, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jul 2026 | Trial primary completion date: Jun 2023 --> Jul 2022
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    bintrafusp alfa (M7824) • Versamune HPV • PDS01ADC
    over1year
    First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma. (PubMed, J Immunother Cancer)
    M9241 plus avelumab was well tolerated at all DLs, including the dose-expansion part, with no new safety signals. However, the dose-expansion part did not meet the predefined efficacy criterion to proceed to stage 2.
    P1 data • Journal • Metastases
    |
    Bavencio (avelumab) • PDS01ADC
    over1year
    Immune correlates with response in patients with metastatic solid tumors treated with a tumor targeting immunocytokine NHS-IL12. (PubMed, Int Immunopharmacol)
    Specific immune analytes at baseline including lower levels of monocytes and plasmacytoid dendritic cells, and early changes after treatment such as an increase in refined NK cell subsets and total CD8+ T cells, associated with better clinical response. These findings may help to guide future schedule and dosing regimens of clinical studies of NHS-IL12 as monotherapy and in combination therapies.
    Clinical Trial,Phase I • Journal • Metastases
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha)
    |
    PDS01ADC
    over1year
    A phase I study of bintrafusp alfa and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic genitourinary (GU) malignancies. (ASCO 2023)
    The use of bintrafusp alfa and M9241 either alone or in combination with sequential or concurrent SBRT has shown clinical activity in pts with GU tumors and has not been associated with any DLTs. Clinical trial information: NCT04235777.
    Clinical • P1 data • Combination therapy • Metastases
    |
    TGFB1 (Transforming Growth Factor Beta 1)
    |
    bintrafusp alfa (M7824) • PDS01ADC
    over1year
    Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
    P2, N=23, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Feb 2023 | Trial primary completion date: Jul 2024 --> Oct 2022
    Trial completion • Trial completion date • Trial primary completion date • Metastases
    |
    MUC1 (Mucin 1) • CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
    almost2years
    Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov)
    P1/2, N=51, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: Jun 2023 --> Jan 2024
    Enrollment closed • Trial completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    bintrafusp alfa (M7824) • Versamune HPV • PDS01ADC
    almost2years
    Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
    P2, N=23, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=80 --> 23
    Enrollment closed • Enrollment change • Metastases
    |
    MUC1 (Mucin 1) • CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
    almost2years
    A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov)
    P1/2, N=80, Recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Aug 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    Jingzhuda (entinostat) • bintrafusp alfa (M7824) • PDS01ADC
    2years
    20-C-0012: Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov)
    P1, N=66, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2023 --> Dec 2023 | Trial primary completion date: Jan 2023 --> Sep 2023
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    bintrafusp alfa (M7824) • PDS01ADC
    2years
    Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial (clinicaltrials.gov)
    P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=20 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 amplification • HER-2 negative • PGR expression
    |
    bintrafusp alfa (M7824) • PDS01ADC
    2years
    T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine M9241 in Localized High- and Intermediate-Risk Prostate Cancer Treated With Androgen Deprivation Therapy (clinicaltrials.gov)
    P2, N=65, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    PDS01ADC
    over2years
    Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov)
    P1/2, N=56, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2023 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    bintrafusp alfa (M7824) • Versamune HPV • PDS01ADC
    over2years
    Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies. (PubMed, J Immunother Cancer)
    Our findings provide a rationale for combining the tumor-targeting NHS-IL12 with the histone deacetylase inhibitor entinostat in the clinical setting for patients unresponsive to αPD-1/αPD-L1 and/or with innate deficiencies in tumor MHC-I, APM expression, and IFN-γ signaling.
    Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CXCL13 (Chemokine (C-X-C motif) ligand 13)
    |
    IFNG expression
    |
    Jingzhuda (entinostat) • PDS01ADC
    over2years
    Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
    P2, N=80, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jul 2023 --> Jul 2024
    Trial primary completion date
    |
    MUC1 (Mucin 1) • CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
    over2years
    T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine M9241 in Localized High- and Intermediate-Risk Prostate Cancer Treated With Androgen Deprivation Therapy (clinicaltrials.gov)
    P2, N=65, Not yet recruiting, National Cancer Institute (NCI)
    New P2 trial • Combination therapy • IO biomarker
    |
    PD-L1 (Programmed death ligand 1)
    |
    PDS01ADC
    over2years
    Preclinical and clinical studies of bintrafusp alfa, a novel bifunctional anti-PD-L1/TGFβRII agent: Current status. (PubMed, Exp Biol Med (Maywood))
    This review thus provides an example of the importance of conducting clinical studies in an appropriate patient population - in this case, exemplified by the role of TGFβ in HPV-associated malignancies. This review also provides preclinical and preliminary clinical study results of the combined use of multiple immune-modulating agents, each designed to engage different immune components and tumor cells in the TME.
    Preclinical • Journal
    |
    TGFB1 (Transforming Growth Factor Beta 1)
    |
    bintrafusp alfa (M7824) • PDS01ADC
    over2years
    Cure of syngeneic carcinomas with targeted IL-12 through obligate reprogramming of lymphoid and myeloid immunity. (PubMed, JCI Insight)
    Study of single-cell data sets from human head and neck carcinomas revealed IL-12 receptor expression patterns similar to those observed in murine tumors. These results describing the diverse mechanisms underlying tumor-directed IL-12-induced antitumor immunity provide the preclinical rationale for the clinical study of i.t. NHS-IL-12.
    Journal
    |
    CD8 (cluster of differentiation 8)
    |
    PDS01ADC
    almost3years
    Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov)
    P1/2, N=56, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jan 2022 --> Jun 2022
    Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    bintrafusp alfa (M7824) • Versamune HPV • PDS01ADC
    almost3years
    NHS-IL12 and bintrafusp alfa combination therapy enhances antitumor activity in preclinical cancer models. (PubMed, Transl Oncol)
    In addition, BA reduced lung metastasis in the 4T1 model. Collectively, these findings could support clinical trials designed to investigate NHS-IL12 and BA combination therapy for patients with advanced solid tumors.
    Preclinical • Journal • Combination therapy
    |
    CD8 (cluster of differentiation 8) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    bintrafusp alfa (M7824) • PDS01ADC
    almost3years
    Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
    P2, N=80, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | N=14 --> 80
    Enrollment open • Enrollment change
    |
    MUC1 (Mucin 1) • CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
    almost3years
    20-C-0012: Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov)
    P1, N=66, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | Trial completion date: Apr 2022 --> Apr 2023 | Trial primary completion date: Jan 2022 --> Jan 2023
    Clinical • Enrollment open • Trial completion date • Trial primary completion date • Combination therapy
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    bintrafusp alfa (M7824) • PDS01ADC
    almost3years
    Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov)
    P1/2, N=56, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | N=21 --> 56
    Enrollment open • Enrollment change
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    bintrafusp alfa (M7824) • Versamune HPV • PDS01ADC
    almost3years
    Phase I/II Trial of the Combination of Bintrafusp Alfa (M7824), Entinostat and NHS-IL12 (M9241) in Patients With Advanced Cancer (clinicaltrials.gov)
    P1/2, N=70, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting
    Enrollment open
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    Jingzhuda (entinostat) • bintrafusp alfa (M7824) • PDS01ADC
    3years
    Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial (clinicaltrials.gov)
    P1, N=20, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Trial completion date: May 2021 --> May 2022 | Trial primary completion date: May 2021 --> May 2022
    Clinical • Enrollment open • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    HER-2 amplification • HER-2 negative • PGR expression
    |
    bintrafusp alfa (M7824) • PDS01ADC
    3years
    20-C-0012: Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies (clinicaltrials.gov)
    P1, N=4, Suspended, National Cancer Institute (NCI) | N=66 --> 4 | Recruiting --> Suspended
    Clinical • Enrollment change • Trial suspension • Combination therapy
    |
    CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    bintrafusp alfa (M7824) • PDS01ADC
    3years
    Phase II Trial of Combination Immunotherapy in Subjects With Advanced Small Bowel and Colorectal Cancers (clinicaltrials.gov)
    P2, N=14, Suspended, National Cancer Institute (NCI) | N=80 --> 14 | Recruiting --> Suspended
    Clinical • Enrollment change • Trial suspension
    |
    MUC1 (Mucin 1) • CD4 (CD4 Molecule)
    |
    bintrafusp alfa (M7824) • Anktiva (nogapendekin alfa inbakicept-pmln) • PDS01ADC • Panvac-VF (falimarev/inalimarev)
    3years
    Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov)
    P1/2, N=21, Suspended, National Cancer Institute (NCI) | N=56 --> 21 | Recruiting --> Suspended
    Clinical • Enrollment change • Trial suspension
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    bintrafusp alfa (M7824) • Versamune HPV • PDS01ADC
    3years
    Phase I/II Trial of the Combination of Bintrafusp Alfa (M7824), Entinostat and NHS-IL12 (M9241) in Patients With Advanced Cancer (clinicaltrials.gov)
    P1/2, N=70, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Clinical • Trial suspension
    |
    PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
    |
    PD-L1 negative
    |
    Jingzhuda (entinostat) • bintrafusp alfa (M7824) • PDS01ADC