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  • American Society of Clinical Oncology (ASCO)  (6)
  • Cheung, Nai-Kong V.  (6)
  • 1
    Online Resource
    Online Resource
    A curative approach to central nervous system metastases of neuroblastoma.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 10545-10545
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 10545-10545
    Abstract: 10545 Background: Neuroblastoma metastatic to the central nervous system (CNS NB) is associated with significant mortality (median survival 〈 6 months, 〈 10% survival at 36 months). Intraventricular compartmental radioimmunotherapy (cRIT) with radio-iodinated murine IgG1 monoclonal antibody 131 I-8H9 targeting tumor cell-surface glycoprotein B7-H3 offers a therapeutic strategy. We analyzed overall survival of patients with CNS NB treated with intraventricular 131 I-8H9 cRIT at Memorial Sloan Kettering Cancer Center (MSK) since 2003. Methods: After radiographic and/or pathologic confirmation of CNS NB, and assessment of adequate CSF flow, cRIT eligible patients underwent treatment on an IRB-approved protocol with either temozolomide/irinotecan-based CNS salvage regimen incorporating craniospinal radiation therapy, 131 I-8H9 cRIT plus systemic immunotherapy (group 1), or non-regimen therapies with 131 I-8H9 cRIT (group 2). cRIT administration involved a 2mCi tracer of 124 I- or 131 I-8H9 with nuclear imaging and CSF sampling for dosimetry followed by 1 or 2 therapeutic injections up to 70 mCi 131 I-8H9. Disease surveillance included serial MR brain/spine, MIBG, CT, and bone marrow evaluation. Data are presented as overall survival after detection of CNS metastasis. Results: 105 patients with CNS NB were evaluated;80 patients (76%) were treated (57 group 1, 23 group 2). Of the 25 patients who were not eligible for cRIT, survival averaged 8.6 months. Of 19 patients with radiographic evidence of disease at the time of cRIT, 7 (36%) demonstrated post cRIT radiographic improvement. At analysis, 45/80 (56%) patients were alive 4.8–152 months (median 58 months) after CNS metastasis, including 36 (45%) at 36 months and 23 (29%) 〉 60 months. Subgroup analyses of 131 I-8H9–treated patients identified age at NB diagnosis (≤18 months), relapse restricted to CNS and group 1 status as factors positively correlated with survival. Conclusions: 76% of patients with CNS NB treated at MSK received 131 I-8H9 cRIT, and approximately half completed multimodality CNS salvage regimen with 131 I-8H9 cRIT. Despite advanced CNS involvement, over 50% of patients treated with 131 I-8H9 cRIT are still alive and nearly 50% have survived at least 36 months. Clinical trial information: NCT00089245.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.10545
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Phase 1 dose-escalation trial using convection-enhanced delivery of radiolabeled monoclonal antibody for diffuse intrinsic pontine glioma following external radiation therapy.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 2010-2010
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2010-2010
    Abstract: 2010 Background: The prognosis of diffuse intrinsic pontine glioma (DIPG) is dire with a median overall survival less than one-year. 124 I-omburtamab is a radiolabeled monoclonal antibody that targets B7-H3 epitope. We evaluated the safety of administering escalating doses and volumes of 124 I-omburtamab via convection-enhanced delivery (CED) in children with DIPG. Methods: MSKCC 11-011 trial is a standard 3+3 phase 1, open-label, dose escalation study in patients with non-progressive DIPG. CED of 124 I-omburtamab was performed between 4-14 weeks post-external radiation therapy. Nine dose levels of a single injection of 124 I-omburtamab (Y-mAbs Therapeutics, USA) (range 0.25 to 8.0 mCi; and volume of infusion (V i ) from 250 to 8,000 µl) have been evaluated so far. Patients were assessed weekly for 30 days. Results: 46 children were evaluable for primary and secondary endpoints. The median age at enrolment was 6.5 years (range 2-17). Two patients have experienced AEs CTCAE grade 3 that were categorized as dose limiting toxicities (DLTs), which led to inclusion of three more patients at both the 4 and 6 mCi dose levels. Eight patients have reported transient AEs of grade 3 considered related to 124 I-omburtamab. The acute grade 3 AEs were generally indicative of nervous system effects due to volume intolerance or radiation injury, and included hemiparesis (n = 3), dysarthria (n = 3), ataxia (n = 3), dysphagia (n = 2), muscular weakness (n = 2) and gait disturbance (n = 1). There were no related AEs CTCAE grade 4 or 5. Estimations of distribution volumes based on T2-weighted imaging were linearly related to volume with a mean volume of distribution/volume of infusion ratio (V d /V i ) between 3 and 3.5. The mean ratio of lesion-to-whole body absorbed dose was ̃1000. Median overall survival from diagnosis across all cohorts was 14.8 months (n = 46, 95% CI 11.5, 16.8) and the survival rate estimates (with 95% confidence intervals) at 1, 2, 3 and 5 years were 0.63 (0.46;0.76); 0.13 (0.05;0.26); 0.08 (0.02;0.19); and 0.04 (0.00;0.16), respectively. Four patients have survived 〉 3 years; two remain alive at 46 and 96 months and two have died at 43 and 53 months, both with CNS disease outside of the treatment field and one with extra-CNS metastases. Conclusions: 124 I-omburtamab via CED into the brain stem of children with DIPG and previously irradiated provides a possibility for improved treatment of DIPG. A dose of 8mCi and an infusion volume of 8,000 µl is considered safe and may provide a distribution volume large enough to cover tumor volumes up to 20 cm 3 . The median overall survival of all patients included in the trial appears to be increased with 3-4 months compared to historical control data from consortia trials. A phase 2 trial aiming at investigating the efficacy of radiolabeled omburtamab administered via CED is being planned. Clinical trial information: NCT01502917.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.2010
    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
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  • 3
    Online Resource
    Online Resource
    A phase I study of convection-enhanced delivery of 124 I-8H9 radio-labeled monoclonal antibody in children with diffuse intrinsic pontine glioma: An update with dose-response assessment.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 2008-2008
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 2008-2008
    Abstract: 2008 Background: Diffuse intrinsic pontine glioma (DIPG) represents one of the most deadly central nervous system tumors of childhood with a median survival of less than 12 months. Convection-enhanced delivery (CED) has been recently hypothesized as a means for efficiently distributing therapeutic agents within the brain stem. We conducted this study to evaluate CED in children with DIPG. Methods: We performed a standard phase I dose escalation study in patients with non-progressive DIPG 4 to 14 weeks post-completion of radiation therapy. Seven dose levels of a single injection of 124 I-8H9 (Omburtamab) (range 0.25 to 4.0 mCi) were studied. Results: 37 children were treated with 34 evaluable for primary and secondary endpoints. The median age at enrollment was 6.8 years old (range 3.2 - 17.9). There was no dose limiting toxicity (DLT). Among adverse events that were at least possibly related to the treatment, there were no grade 4 or 5 events, and only 4 reversible grade 3 events in 4 patients (2 hemiparesis, 1 skin infection and 1 anxiety). Estimations of distribution volumes based on T2-weighted imaging were dose dependent and ranged from 1.5 to 20.8 cm 3 , and for dose level 7, 10.5 - 19.0 cm 3 . The mean volume of distribution/volume of infusion ratio (Vd/Vi) was 3.4 ±1.1, and for dose level 7, 3.5 ± 1.0. The mean lesion absorbed dose was 33.3 ± 25.9 Gy, and for dose level 7, 50.1 ± 22.9 Gy. The mean ratio of lesion-to-whole body absorbed dose was 910. The mean volume of distribution/tumor volume ratio on dose level 7 was 82.5%, but the mean tumor overlap was 40.5%. No death occurred as a result of the treatment. Median survival was 15.3 months (n = 29, 95% CI 12.7 - 17.4). Median follow-up time of the 5 surviving patients is 27.2 months (range 11.5 - 72.4). Overall survival rate at 12 months was 64.7% (22/34, 4 alive), and overall survival rate at 24 months 14.7% (5/34, 3 alive). Conclusions: CED in the brain stem of children with DIPG who were previously irradiated is a safe therapeutic strategy. An infusion volume of 4,000 mcl appears to be a reasonable single dose for a target distribution volume but enhanced tumor coverage is likely needed. There seems to be a survival benefit using this therapeutic strategy and outcomes might be dependent on dosimetry and distribution patterns. Clinical trial information: NCT01502917.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.2008
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    Intraventricular radioimmunotherapy targeting B7H3 for CNS malignancies.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13592-e13592
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13592-e13592
    Abstract: e13592 Background: Tumors metastasizing to the central nervous system (CNS) are associated with significant mortality. We tested the toxicity and dosimetry of intraventricular 131 I-labeled monoclonal antibody 8H9 targeting surface glycoprotein B7-H3 in patients with primary or metastatic CNS tumors. Methods: Tumor B7-H3 expression was assessed by immunohistochemistry. CSF flow was determined by 111 Indium-DTPA cisternography. 131 patients received 2 mCi tracer of intra-Ommaya 124 I- or 131 I-8H9 for nuclear imaging followed by a therapeutic injection (10-80 mCi, dose levels 1-8 in 10 mCi increments for phase I patients; expanded cohort 50 mCi/injection) 131 I-8H9. Pharmacokinetics were studied by serial CSF and blood samplings over 48 hours. Dosimetry was based on pharmacokinetics and region of interest analyses on serial PET. Toxicity was defined by the CTCAE v.3.0. 8H9 dosimetry and therapy injections were repeated after 1 month if no serious adverse events or progressive disease ensued. Tumor response was determined by clinical, radiographic, cytologic criteria; overall survival was noted. Results: 57 patients (ages 2 – 54 years, median age 11.7 years) received 158 injections Primary CNS diagnoses included medulloblastoma (n = 23), ependymoma (N = 8), chordoma (n = 1), rhabdoid tumor (n = 1), choroid plexus carcinoma (n = 3), ETMR (n = 3), glioblastoma multiforme (n = 1) , PXA (n = 1); metastatic tumors included sarcoma (n = 9), melanoma (n = 4), retinoblastoma (n = 2), and ovarian carcinoma (n = 1). Injections were well tolerated and routinely administered in the outpatient setting. Rare self-limited adverse events included grade 1 or 2 fever, headache, vomiting; 3 injections were associated with grade 3 toxicities requiring discontinuation of therapy including chemical meningitis (n = 2),and increasing communicating hydrocephalus (n = 1), Although not a dose limiting toxicity, myelosuppression occurred in patients who had received craniospinal radiation and at dose levels 6 and higher (≥60 mCi). 16 patients remain alive including patients with high-risk malignancies including choroid plexus carcinoma, ETMR, recurrent ependymoma and recurrent medulloblastoma. Conclusions: We conclude that intraventricular 131 I-8H9 is safe, has favorable dosimetry to CSF, and may have clinical utility in the treatment of primary and metastatic CNS tumors. Clinical trial information: NCT00089245.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13592
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    A phase I study of convection enhanced delivery (CED) of 124 I-8H9 radio-labeled monoclonal antibody in children with diffuse intrinsic pontine glioma (DIPG).
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 2010-2010
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 2010-2010
    Abstract: 2010 Background: Diffuse intrinsic pontine glioma (DIPG) represents one of the most deadly central nervous system tumors of childhood with a median survival of less than 12 months. Convection-enhanced delivery (CED) has been recently hypothesized as a means for augmenting distribution of therapeutic agents within the brain stem. We conducted this study to evaluate CED in children with DIPG. Methods: We performed a standard 3+3 phase I, open-label, dose escalation study in patients with non-progressive DIPG 4 to 14 weeks post-completion or radiation therapy. Seven dose levels of a single injection of 124 I-8H9 (range 0.25 to 4.0 mCi, 250 to 4000 mcl) were studied. Results: 25 children were treated. The average age at enrollment 8 years old (range 3-17). There was no dose limiting toxicity (DLT) and adverse events were limited to grade 1 or 2 (CTCAE v4.0). Estimations of distribution volumes were dose dependent and ranged from 1.5 to 20.1 cm 3 . The mean volume of distribution/volume of infusion (Vd/Vi) was 3.4 (SD 1.2). The mean lesion absorbed dose was 1527 rad/mCi. The mean tumor coverage on dose level 7 was 107%. Conclusions: CED in the brain stem of children with DIPG who were previously irradiated is a safe therapeutic strategy. Up to 4 mCi of 124 I-8H9 was well tolerated. An infusion volume of 4000 mcl appears to be a reasonable single dose for good tumor coverage. PET-based dosimetry validates the conceptual basis for direct drug delivery. Based on our finding CED merits further exploration in early phase clinical trials for children with DIPG. Clinical trial information: NCT01502917.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.2010
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 6
    Online Resource
    Online Resource
    Naxitamab-based chemoimmunotherapy for resistant high-risk neuroblastoma: Results of "HITS" phase II study.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 10028-10028
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 10028-10028
    Abstract: 10028 Background: Chemoresistant disease is an obstacle for cure of high-risk neuroblastoma (HR-NB). Anti-GD2 monoclonal antibodies (MoAb) dinutuximab and naxitamab in combination with cytokines are FDA-approved to consolidate remission and for chemorefractory osteomedullary HR-NB, but responses in progressive disease (PD) are rare. We investigated the combination of Humanized anti-GD2 MoAb naxitamab (Hu3F8), Irinotecan, Temozolomide and Sargramostim (GMCSF) in a phase II "HITS" protocol against resistant HR-NB (NCT03189706). Noteworthy differences between HITS and COG protocol ANBL 1221 included higher MoAb and temozolomide dosage and overlap of naxitamab with GMCSF. Methods: Patients were treated at Memorial Sloan Kettering (MSK) on protocol and at Hospital Sant Joan de Déu (HJSD) per protocol on compassionate basis. Salient eligibility criteria included evaluable or measurable chemoresistant disease. Prior anti-GD2 MoAb or irinotecan/temozolomide (IT) therapy was permitted. Each cycle, administered 3-5 weeks apart, comprised irinotecan 50 mg/m 2 /day intravenously (IV) plus temozolomide 150 mg/m 2 /day IV or orally (days 1-5); naxitamab 2.25 mg/kg/day IV, days 2,4,8 and 10, and GMCSF 250 mg/m 2 /day subcutaneously, days 6-10. Toxicity was measured by CTCAE v4.0 and responses by International Neuroblastoma Response Criteria. Objective responses (OR) were also noted. The primary endpoint of the phase II trial was complete (CR) and partial response (PR) after 4 cycles with a desirable rate of 40%; type I and II errors of 10% (undesirable=20%). Results: Of 90 heavily prior-treated patients (38 at MSK evaluated on trial, 52 at HJSD), 8 had HR-NB refractory to induction chemotherapy while 82 had up to 6 prior relapses (median=1). 503 cycles (median 5/patient) were administered. Toxicities included myelosuppression and diarrhea expected with IT, pain and hypertension expected with naxitamab, plus febrile neutropenia in 4%. No other 〉 grade 2 unexpected toxicities occurred; treatment was outpatient. Primary endpoint was reached in the phase II trial: INRC response = 30.6%, lower boundary = 20.4%. In the entire cohort, best responses were CR (26%), PR (11%), mixed response (9%), stable disease (27%) and PD (27%). OR were noted in 64%, with soft tissue (48%) and skeletal MIBG uptake (66%). CR in BM was seen in 57%. OR occurred in patients with MYCN-amplified (25%), refractory (100%) and relapsed (61%) HR-NB; and patients who had previously received I/T (64%) or naxitamab (68%). In patients who had previously received dinutuximab/IT, OR rate to HITS was 42% (5/12). Human anti-human antibody did not develop in any patient (n=50). Conclusions: Naxitamab-based chemoimmunotherapy was safe without immunogenicity. It was effective against chemoresistant HR-NB in all disease compartments even in patients with multiple prior relapses, and in patients who previously received anti-GD2 MoAbs and/or IT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.10028
    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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