Inclusion Criteria:

          -  M/F at least 18 years old

          -  ECOG performance status 0 or 1

          -  Adequate bone marrow, liver, and kidney function within 2 weeks prior to first dose

          -  Serum potassium, calcium, magnesium, phosphorus within normal limits (may be
             supplemented)

          -  Adequate birth control

          -  Somatostatin receptor 2 positive tumor as assessed at pre-screening or within 180 d of
             first drug dose using indium SPECT or gallium PET

        Patients in Phase 1 must have a histologically or cytologically-confirmed solid tumor in 1
        of the following categories:

          -  Advanced small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC)
             of lung progressed after at least 1 line of anticancer chemotherapy

          -  Advanced low or intermediate grade gastroenteropancreatic or lung or thymus
             neuroendocrine tumor (NET), or NET of unknown primary, progressed after at least 1
             line of anticancer therapy (unless no standard treatments available or such treatments
             are deemed not appropriate)

          -  Advanced paraganglioma, pheochromocytoma, medullary thyroid carcinoma, Merkel cell
             carcinoma, or high grade extrapulmonary neuroendocrine carcinoma having progressed
             after 1 or more lines of anticancer chemotherapy (unless no standard treatments
             available or such treatments are deemed not appropriate)

        For patients enrolling once escalation is complete (Phase 2a), disease must be measurable
        per RECIST 1.1 criteria with last imaging performed within 28 days prior to first drug dose

        In addition to the criterion listed above, Patients in Phase 2a must have a histologically-
        or cytologically-confirmed, advanced or metastatic solid tumor, in 1 of the following
        categories: disease history specified in one of the criteria listed below:

          -  Well differentiated, low or intermediate grade, gastrointestinal mid-gut (arising from
             the lower jejunum, ileum, appendix, cecum, and proximal colon) NET with documented
             disease progression within 6 months prior to start of study treatment and evidence of
             radiographic disease progression based on scans performed not more than 15 months
             apart. Patients may have received 1 or more prior lines of anticancer therapy, such as
             somatostatin analogues, targeted agents, or liver-directed intra-arterial therapy, but
             are NOT eligible if they have received prior systemic cytotoxic chemotherapy.

          -  Well differentiated, low or intermediate grade, pancreatic NET with documented disease
             progression within 6 months prior to start of study treatment and evidence of
             radiographic disease progression based on scans performed not more than 15 months
             apart. Patients may have received 1 or more prior lines of anticancer therapy, such as
             somatostatin analogues, targeted agents, or liver-directed intra-arterial therapy, and
             up to 1 prior line of systemic cytotoxic chemotherapy, but are NOT eligible if they
             have received more than 1 prior line of systemic cytotoxic chemotherapy or if they
             have received prior peptide receptor radionuclide therapy (PRRT)

          -  SCLC after having received up to three prior lines of anticancer therapy.

        Exclusion Criteria:

          -  Treatment with anticancer therapy or investigational drug or device within 3 wk (6 wk
             for nitrosureas or mitomycin C) or 5 half-lives of agent, whichever is shorter, prior
             to first PEN-221 drug dose, and any drug-related toxicities must have recovered to
             grade 1 or less

          -  Any other malignancy known to be active or treated within 3 years of start of
             screening, except cervical intra-epithelial neoplasia, superficial (non-invasive)
             bladder cancer, and non-melanoma skin cancer

          -  Cardiac criteria such as unstable angina, myocardial infarction within 6 months of
             screening, NY Heart Association Class 1 or 2 heart failure, QTc greater than 470 msec,
             congenital long Qt syndrome, symptomatic orthostatic hypotension within 6 months of
             screening, uncontrolled hypertension, or clinically important abnormalities in heart
             rhythm, conduction, morphology of resting ECG

          -  Stroke or transient ischemic attack within 6 months of screening

          -  Peripheral neuropathy greater than grade 1

          -  Requirement for medication with strong CYP3A4 inhibitor

          -  History of leptomeningeal disease or spinal cord compression

          -  Brain metastases unless asymptomatic on a stable low dose of steroids. Patients with
             SCLC or LCNEC of lung only must have CT or MRI of brain during screening, and if
             metastases found, must have radiotherapy with 14 day washout or stereotactic
             radiotherapy or radio surgery with 7 day washout prior to first drug dose.

          -  Major surgery within 28 days of first drug dose

          -  Female who is pregnant or breast feeding

          -  Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver
             transplant, active infection with hepatitis B or C, or HIV

          -  Hypersensitivity or anaphylactic reaction to any somatostatin analog or to
             maytansinoids