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  • 1
    Online Resource
    Online Resource
    Combining IL-12 immunocytokine (M9241) with docetaxel in metastatic prostate cancer: A phase I study.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e17033-e17033
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e17033-e17033
    Abstract: e17033 Background: M9241 is an immunocytokine that targets single- and double-stranded DNA which allows the treatment to localize IL-12 to necrotic tumor (Xu, CCR 2017). M9241 was well-tolerated as a monotherapy in a Phase I study with solid tumors (Strauss J, CCR 2019). Additional preclinical data has demonstrated synergy of M9241 with cytotoxic therapy. This is the first study to examine the safety of a novel combination of chemotherapy and immunocytokines in metastatic prostate cancer. Methods: This safety analysis included patients with mCSPC or mCRPC. Patients were enrolled in a 2-dose level (DL) escalation cohort of M9241 (DL 1: 12mcg/kg, DL 2: 16.8mcg/kg) combined with docetaxel (75mg/m 2 ) with 6 patients planned per DL. A third DL of 8mcg/kg will enroll 6 more patients after the 16.8mcg/kg DL has fully enrolled. All patients were treated with ADT. Patients were initiated on treatment with docetaxel with a plan for mCSPC patients to receive six 3-week cycles of combined treatment and mCRPC patients to continue until progression or unacceptable toxicity. M9241 was given starting with the second cycle of treatment for each patient. Dose-limiting toxicity (DLT) was evaluated in the first 6 weeks after start of docetaxel (from cycle 1 day 1 through the end of the first cycle with M9241). Results: The study has enrolled 10 patients out of a planned 18 for the safety portion. Age range is 58-82 with a median of 69 years. Race distribution is 80% White and 20% Black. Gleason scores for patients were 8 (40%), 9 (40%), and 10 (20%). No DLTs were seen with either dose-level. Only 1 patient had a Grade 4 AE, neutropenia. Grade 3 toxicities included anemia, diarrhea, leukopenia, and hypotension (each occurring in 10% of the patients). The most frequent adverse events (AEs) of any grade were anemia (40%) and lymphopenia (40%), followed by fatigue (30%), diarrhea (20%), and fever (20%). Conclusions: We established a safe dose-level of M9241 at ≥ 12mcg/kg. Updated clinical data from the safety cohort (n = 18) will be presented. This demonstrates that an immunocytokine and chemotherapy can be safely combined for treatment in metastatic prostate cancer. Two planned expansion cohorts will evaluate docetaxel and M9241 in mCSPC and mCRPC, respectively. Clinical trial information: NCT04633252.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e17033
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Safety evaluation of M9241 in combination with docetaxel in metastatic prostate cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 93-93
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 93-93
    Abstract: 93 Background: M9241 is an immunocytokine that targets single- and double-stranded DNA which allows the treatment to localize IL-12 to necrotic tumor (Xu, CCR 2017). M9241 was well-tolerated as a monotherapy in a Phase I study with solid tumors (Strauss J, CCR 2019). Additional preclinical data has demonstrated synergy of M9241 with cytotoxic therapy. This is the first study to examine the safety of a novel combination of chemotherapy and immunocytokines in metastatic prostate cancer. Methods: This safety analysis included patients with mCSPC or mCRPC. Patients were enrolled in a 2-dose level (DL) escalation cohort of M9241 (DL 1: 12mcg/kg, DL 2: 16.8mcg/kg) combined with docetaxel (75mg/m 2 ) with 6 patients planned per DL. A third DL of 8mcg/kg will enroll 6 more patients after the 16.8mcg/kg DL has fully enrolled. All patients were treated with ADT. Patients were initiated on treatment with docetaxel with a plan for mCSPC patients to receive six 3-week cycles of combined treatment and mCRPC patients to continue until progression or unacceptable toxicity. M9241 was given starting with the second cycle of treatment for each patient. Dose-limiting toxicity (DLT) was evaluated in the first 6 weeks after start of docetaxel (from cycle 1 day 1 through the end of the first cycle with M9241). Results: The study has enrolled 10 patients out of a planned 18 for the safety portion. Age range is 58-82 with a median of 69 years. Race distribution is 80% White and 20% Black. Gleason scores for patients were 8 (40%), 9 (40%), and 10 (20%). No DLTs were seen with either dose-level. Only 1 patient had a Grade 4 AE, neutropenia. Grade 3 toxicities included anemia, diarrhea, leukopenia, and hypotension (each occurring in 10% of the patients). The most frequent adverse events (AEs) of any grade were anemia (40%) and lymphopenia (40%), followed by fatigue (30%), diarrhea (20%), and fever (20%). Conclusions: We established a safe dose-level of M9241 at ≥ 12mcg/kg. Updated clinical data from the safety cohort (n = 18) will be presented. This demonstrates that an immunocytokine and chemotherapy can be safely combined for treatment in metastatic prostate cancer. A planned expansion cohort will evaluate docetaxel and M9241 in mCRPC. Clinical trial information: NCT04633252.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.093
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    A phase I/II study of bintrafusp alfa and NHS-IL12 in combination with docetaxel in adults with metastatic castration sensitive (mCSPC) and castration-resistant prostate cancer (mCRPC).
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS5096-TPS5096
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS5096-TPS5096
    Abstract: TPS5096 Background: Immune checkpoint inhibition is successful in a small subpopulation of men with prostate cancer. This could be related to barriers to immune response in the tumor microenvironment. Immunocytokines present an opportunity to specifically target the pleiotropic tumor microenvironment impacting immune cells beyond T-cells. NHS-IL12 is an immunocytokine that carries IL-12 (shown to impact natural killer and myeloid cells) and binds to necrotic tissue with exposed histones. Phase 1 studies have indicated immune and even PSA responses in prostate cancer to NHS-IL12 (Strauss J, CCR 2019). Preclinical data has demonstrated synergy with docetaxel, which is standard therapy in both mCSPC and mCRPC. Further synergy has been shown with a novel first-in-class bifunctional fusion protein (bintrafusp alfa) composed of the extracellular domain of human TGF-β receptor II (TGFβRII), which effectively functions to sequester or “trap” all three TGF-β isoforms (Lind H, JITC 2020), fused to a monoclonal antibody against PD-L1. This study will examine the potential of a novel combination of chemotherapy, checkpoint inhibition, and immunocytokines in metastatic prostate cancer. Methods: The study will evaluate safety of NHS-IL12 with docetaxel at escalating doses followed by the addition of bintrafusp alfa in all metastatic patients. Once safety of the combination is established, patients will enroll in 2 cohorts with either mCSPC or mCRPC. Eligible patients include mCSPC (≤134 days of starting ADT) and mCRPC (must have been previously treated with abiraterone or enzalutamide), with good performance status (ECOG of ≤ 2). Patients with brain metastases or who are immunocompromised are excluded. For mCSPC, the primary endpoint will evaluate the increase in the proportion of patients who have a PSA less than 0.2 ng/mL 7 months after the start of ADT, which is based on the prognostic value of PSA less than 0.2 ng/mL at 7 months in mCSPC (Harshman L, JCO 2017). The secondary endpoint is biochemical and radiographic time to progression. The primary endpoint for the mCRPC patients will evaluate progression free survival with secondary endpoints examining the percentage of patients with a 50% PSA decline from baseline and radiographic response rates per RECIST. Exploratory analysis will analyze changes in immune cell subsets after treatment as well as immune status of the tumor microenvironment. Clinical trial information: NCT04633252.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.TPS5096
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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