Patients with ipsilateral axillary lymph node-negative disease, regardless of metastatic status (Stages T1-4 N0 M0-1)

Radiation with 26Gy to the whole breast and 40Gy simultaneous integrated boost to gross disease in the breast, in five fractions

Whole breast radiation with simultaneous integrated boost (WB-SIB) to primary breast tumor

Patients with ipsilateral axillary node-positive disease, regardless of metastatic status (Stages T1-4 N1-2 M0-1)

Radiation with 26Gy to the whole breast and regional nodes with a 40Gy simultaneous integrated boost to gross disease in breast and ipsilateral axillary nodal areas, in five fractions

Whole breast radiation with simultaneous integrated boost (WB-SIB) to primary breast tumor and ipsilateral axillary lymph nodes

Ravi Kanani

Stony Brook Cancer Center Clinical Trials Office

Alexander Stessin, MD PhD

The recurrent, progressive, or refractory primary malignant non-brainstem CNS tumor patients will be treated with APX005M.

APX005M dosing will begin at 0.1 mg/kg, the APX005M dose may be increased (0.3, 0.45, 0.6 mg/kg) or decreased (0.03 mg/kg) in subsequent cohorts until the maximum tolerated dose (MTD) is reached or until dose level 3 (0.6 mg/kg) is complete without the MTD being defined.

APX005M will be administered at the assigned dose level every 21 days (3 weeks). Patients may continue to receive APX005M for 36 courses (approximately 2 years) or until disease progression, unacceptable toxicity or death, whichever occurs first.

APX005M treatment for recurrent or refractory primary malignant CNS tumor patients

The newly diagnosed diffuse intrinsic pontine gliomas (DIPGs) patients will be treated with APX005M.

The starting dose of APX005M for the DIPG patients will be one dose level below the recommended phase II dose (RP2D) determined in Stratum 1 patients. The dose may be decreased or increased to the RP2D established in Stratum 1.

APX005M will be administered at the assigned dose level every 21 days (3 weeks). Patients may continue to receive APX005M for 36 courses (approximately 2 years) or until disease progression, unacceptable toxicity or death, whichever occurs first.

APX005M treatment for newly diagnosed DIPG patients

Upper endoscopy with RP2 intra-tumoral injection of 1 x 10(6) plaque forming units (PFU)/mL for first intra-tumoral injection, up to 10mL of 1x107 PFU/mL of RP2 for subsequent intra-tumoral injections. Injection will occur within 4 days prior of each cycle FLOT.

5-Fluorouracil as part of the FLOT regimen 2,600mg/m2 intravenous infusion over 24 hours on day 1 of each 14-day cycle for 4 cycles.

5-Fluorouracil

Leucovorin as part of the FLOT regimen 200mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

Leucovorin

Oxaliplatin as part of the FLOT regimen 85mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

Oxaliplatin

Docetaxel as part of the FLOT regimen 50mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

Docetaxel

Pegfilgrastim or Filgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

Pegfilgrastim

Filgrastim or Pegfilgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

Filgrastim

Following 4 cycles of preoperative FLOT with RP2 injections, surgical resection of esophageal, GEJ, or gastric primary tumor per standard of care practice.

Surgical Resection of Primary Tumor

Jennifer Walsh

William Chapin, MD, MSCE

Oncolytic Virus: Administered via intratumoral (metastatic lesions in the neck or supraclavicular lymph nodes) injection once every 3 weeks, for a total of two doses, or until disease progression, the occurrence of unacceptable toxicity, or death from any cause, whichever occurs first.Chemotherapy + Immune Checkpoint Inhibitor (ICI): Administered via intravenous infusion once every 3 weeks.

Oncolytic Virus: Administered via intratumoral injection(metastatic lesions in the neck or supraclavicular lymph nodes) once every 3 weeks, for a total of two to four doses, or until disease progression, the occurrence of unacceptable toxicity, or death from any cause, whichever occurs first. Chemotherapy + Immune Checkpoint Inhibitor (ICI): Administered via intravenous infusion once every 3 weeks.

Oncolytic Virus: Administered via intratumoral injection (metastatic lesions in the neck or supraclavicular lymph nodes) once every 3 weeks, for a total of two to four doses.

Oncolytic Virus: Administered via intratumoral (primary lesion of ESCC) injection once every 3 weeks, for a total of two doses, or until disease progression, the occurrence of unacceptable toxicity, or death from any cause, whichever occurs first.Chemotherapy + Immune Checkpoint Inhibitor (ICI): Administered via intravenous infusion once every 3 weeks.

Oncolytic Virus: Administered via intratumoral injection (primary lesions) once every 3 weeks, for a total of two to four doses, , or until disease progression, the occurrence of unacceptable toxicity, or death from any cause, whichever occurs first. Chemotherapy + Immune Checkpoint Inhibitor (ICI): Administered via intravenous infusion once every 3 weeks.

원발성 유방 종양에 대한 동시 통합 부스트(WB-SIB)를 포함한 전체 유방 방사선 치료, 원발성 유방 종양 및 동측 액와 림프절에 대한 동시 통합 부스트(WB-SIB)를 포함한 전체 유방 방사선 치료

재발성 또는 내성성 원발성 악성 중추신경계 종양 환자를 위한 APX005M 치료, 신규 진단된 DIPG 환자를 위한 APX005M 치료

RP2, 5-플루오로우라실, 류코보린, 옥살리플라틴, 도세탁셀, 페그필그라스팀, 필그라스팀, 원발성 종양의 외과적 절제

용종용해성 바이러스: 3주에 한 번씩 종양 내 주사(목이나 쇄골 위 림프절의 전이성 병변)를 통해 총 2~4회 투여합니다. 용종용해성 바이러스: 3주에 한 번씩 종양 내 주사(원발성 병변)를 통해 총 2~4회 투여합니다.