• Histologically or cytologically confirmed high-grade neuroendocrine tumor that has progressed after at least one line of therapy, excluding small cell lung cancer (SCLC). High grade includes any neuroendocrine neoplasm with a Ki-67 of \>=20% or with mitotic count of more than 20 mitoses per high power field or any poorly differentiated neoplasm or any neoplasm lacking these that is deemed high grade by pathology consensus, based on other markers (necrosis or IHC demonstrating p53 or RB mutation). This includes:

⁃ High grade well differentiated neuroendocrine neoplasms

⁃ Transformed NENs from a lower to a higher grade (patient may have some low grade and some high grade NENs)

⁃ High grade neoplasms with significant expression of neuroendocrine markers such as synaptophysin, chromogranin or INSM-1 or unknown origin neoplasms with gene expression signatures consistent with neuroendocrine lineage (as per validated tissue of origin testing, such as CancerType ID, after pathology consensus).

⁃ Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNEN), including MiNEN per WHO and mixed neoplasms not fulfilling criteria of MiNEN. The neuroendocrine component would need to be a high-grade neuroendocrine tumor as documented by pathology review.

• Note: Up to two prostate NEC patients (primary diagnosis, not transformed adenocarcinoma) will be enrolled in the first phase. For the second phase, non gastroenteropancreatic or lung histologies will be approved by PI.

• Note: For ambiguous cases, will consult with a designated expert pathologist.

⁃ Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.

⁃ Concurrent or prior somatostatin analogue therapy is allowed (for well differentiated high grade neoplasms). Prior use of investigational agents is allowed.

⁃ At least 18 years of age.

⁃ ECOG performance status ≤ 1 (Karnofsky ≥ 80%)

⁃ Normal bone marrow and organ function as defined below:

∙ Absolute neutrophil count ≥ 1,500/mm3 without granulocyte colony-stimulating factor support

‣ White blood cell count ≥ 2,500/mm3

‣ Platelets ≥ 100,000/mm3 without transfusion

‣ Hemoglobin ≥ 9.0 g/dL

‣ AST(SGOT), ALT(SGPT), and alkaline phosphatase (ALP) ≤ 3.0 x IULN; ALP ≤ 5.0 x IULN with documented bone metastases

‣ Total bilirubin ≤ 1.5 x IULN (for subjects with gilbert's disease ≤ 3.0 x IULN)

‣ Serum albumin ≥ 2.8 g/dL

‣ Serum creatinine ≤ 2.0 x IULN or calculated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault

‣ Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)

‣ PT/INR or PTT \< 1.3 x IULN (within 7 days before the first dose of study treatment)

⁃ Corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms (by ECG)

⁃ Recovery to baseline or ≤ grade 1 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable on supportive therapy as per discussion with PI.

⁃ Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.

⁃ Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause).

⁃ Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

⁃ Willing to undergo 3 mandatory biopsies: in screening, on treatment prior to C2, and at EOT, if safe and feasible.