Inclusion Criteria:
1. 18 years or older and able to sign informed consent and comply with the protocol.
2. Measurable disease as defined by RECIST v1.1 criteria for solid tumors.
3. Part A and B: patients with histologically or cytologically confirmed unresectable
advanced or metastatic small cell lung cancer (SCLC), large cell neuroendocrine
carcinoma of the lung (LCNEC) or extrapulmonary neuroendocrine carcinoma (EP-NEC),
including but not limited to neuroendocrine prostate cancer (NEPC) and
gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC), previously treated with
standard of care treatments (at least one line of platinum-based chemotherapy with or
without immune checkpoint inhibitor for SCLC patients), and progressed after
treatment, or for which treatment is not available or not tolerated. Treatment for
limited stage disease qualifies as a line of therapy. SCLC that transformed from an
EGFR mutant NSCLC are eligible for this study, given they meet the above criteria.
4. Parts A and B: patients with tumors that are of mixed histologies for any above type
are eligible only if neuroendocrine carcinoma/small tumor cells component is
predominant and represents at least 50% of the overall tumor tissue.
5. Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample
(preferably a fresh biopsy, or if not possible, archival tissue) to be assessed for
DLL3 expression and other biomarkers. Biopsy must be excisional, incisional, or core
needle. Fine needle aspiration is insufficient. Archival tissue is acceptable if
biopsy was completed within 12 months, discuss with Medical Monitor if this is not
feasible, for any potential exceptions. This biopsy may not be done if the biopsy
poses a risk to the patient and/or per the Investigator's discretion.
6. ECOG performance status of 0 or 1.
7. Adequate organ function confirmed at screening and within 72 hours of initiating
treatment, as evidenced by:
- - Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
- - Hemoglobin (Hgb) ≥ 9.0 g/dL (RBC transfusions not permitted in the 4-week period
before enrollment)
- Platelets (plt) ≥ 100 × 109/L.
- - AST/SGOT and ALT/SGPT ≤ 2.5 × Upper Limit of Normal (ULN) or ≤ 5.0 × ULN if liver
metastases are present.
- - Total bilirubin ≤ 1.5 × ULN without liver metastases or < 3.0 x ULN if liver
metastases are present.
- - Calculated creatinine clearance ≥ 30 mL/min (Cockcroft Gault formula)
8.
Resolution of all acute adverse events resulting from prior cancer therapies to
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE
v5.0) Grade ≤ 1 or baseline (except alopecia or neuropathy in Parts A and B ).
9. Negative serum pregnancy test within 72 hours before starting study treatment in all
women of child-bearing potential, including pre-menopausal women, and women < 24
months after the onset of menopause (had a menstrual period in past 24 months) Women
who underwent hysterectomy or bilateral oophorectomy do not need a pregnancy test.
10. Must agree to use effective contraceptive methods to avoid pregnancy (including male
and female patients and partners of study patients) during the study and until at
least 7 months after receiving the last dose of study treatment.
11. Life expectancy >3 months.
Exclusion Criteria:
1. Women who are pregnant or lactating.
2. Women of child-bearing potential (WOCBP) who do not use adequate birth control.
3. Autoimmune disease requiring systemic treatment within the past twelve months.
4. Condition requiring systemic treatment with either corticosteroids or other
immunosuppressive medications within 14 days prior to study treatment. Corticosteroid
doses equivalent to Prednisone 10 mg per day or less are allowed, or a single
application of up to 8 mg Dexamethasone as optional pretreatment for the first two
dose applications of PT217 (from Dose Level 3). .
5. Patients who have experienced Grade ≥ 3 immune-related events, such as
(non-infectious) pneumonitis, interstitial lung disease, myocarditis. Patients who
have experienced Grade < 3 immune-related events that have been resolved for > 6
months, are eligible.
6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (e.g., biweekly or more frequently pericardiocentesis or
thoracentesis).
7. Patients with untreated brain or central nervous system (CNS) metastases or brain/ CNS
metastases that have progressed (e.g., evidence of new or enlarging brain metastasis
or new neurological symptoms attributable to brain/ CNS metastases).
Note: Patients with treated brain metastases that are off corticosteroids and have
been clinically stable for 14 days are eligible for enrollment.
8. Patients with a known concurrent malignancy that is progressing or has required
treatment for active disease within the previous 24 months. Exceptions include basal
cell carcinoma of the skin, carcinoma in situ of the cervix or other noninvasive or
indolent malignancies that have either previously undergone potentially curative
therapy or don't have active treatment indication (e.g., low grade prostate cancer).
9. Patients who have received an investigational product, within 4 weeks or 5 half-lives,
whichever is shorter, prior to start of study drug or who have not recovered from
adverse events of prior therapy, either in the metastatic or adjuvant setting.
10. Prior treatment with T-cell engager, CAR-T, NK cell engager, CAR-NK, DLL3 or CD47
targeting therapies, or anti-SIRPα (signal regulatory protein alpha) targeting agents
(prior Checkpoint inhibitor anti PD-1 and anti PD-L1 therapies are allowed).
11. Patients that have received a live-virus vaccination within 30 days of planned
treatment start.
12. Impaired cardiac function or significant diseases, including but not limited to any of
the following:
1. LVEF < 45% as determined by MUGA scan or ECHO. 2. Congenital long QT syndrome. 3. QTcF ≥ 480 msec on screening ECG. 4. Unstable angina pectoris ≤ 3 months prior to starting study drug.
5. Acute myocardial infarction or stroke ≤ 3 months prior to starting study drug.
13. Patients with uncontrolled hypertension.
14. Prior hemolytic anemia or Evans Syndrome in the last 3 months.
15. RBC transfusion during the 4-week period prior to enrollment. RBC transfusions are not
permitted during the screening period and prior to enrollment to meet the hemoglobin
inclusion criteria.
16. Patients who have ≥ Grade 3 neuropathy.
17. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active infection
requiring parenteral treatment) that could cause unacceptable safety risks or
compromise compliance with the protocol.
18. Patients who have received chemotherapy or small molecule targeted therapy, ≤ 5
half-lives or 3 weeks, whichever is shorter (6 weeks for nitrosourea or mitomycin-C),
other targeted therapy, or immunotherapy within 4 weeks prior to starting study drug.
Concurrent use of hormone deprivation therapy for hormone refractory prostate cancer
is permitted; patients on a stable bisphosphonate or denosumab for ≥ 30 days prior to
study day 1 are eligible.
19. Patients who have received wide field radiotherapy ≤ 2 weeks prior to starting study
drug or who have not recovered from adverse events of prior therapy.
20. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or
who have not recovered from adverse events of prior therapy.
21. Patients who are currently receiving treatment with therapeutic doses of warfarin
sodium (Coumadin®) or any other coumarin-derivative anticoagulants (other
anticoagulants such as anti-thrombin or factor X inhibitors are allowed as long as
patients are on a stable dose).
22. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
mandatory; patients with well controlled HIV might be enrolled per Investigator's
discretion).
23. Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately
controlled. (For patients with known prior history of Hepatitis B or Hepatitis C,
enrollment may be allowed per Investigator's discretion). Note: No testing for
Hepatitis B and Hepatitis C is required unless mandated by a local health authority.
- - Patients who are HBsAg positive are eligible if they have received HBV antiviral
therapy for at least 4 weeks and have undetectable HBV viral load prior to
treatment.
Patients should remain on anti-viral therapy throughout study
intervention and follow local guidelines for HBV anti-viral therapy post
completion of study intervention.
- - Patients with history of HCV infection are eligible if HCV viral load is
undetectable at screening.
Patients must have completed curative anti-viral
therapy at least 4 weeks prior to treatment.
24. Has a history or current evidence of any medical or psychiatric condition, therapy, or
laboratory abnormality that, in the opinion of the Investigator, might confound the
results of the trial, interfere with the patient's safe participation and compliance
in the trial. For example, conditions that depend on the establishment of collateral
circulation, such as peripheral arterial vascular disease, myocardial infarction
recovery period, etc.
25. Has allergies or hypersensitivity to polysorbate 80, L-Histidine or Sucrose (PT217
inactive ingredients).
