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. Histologically or cytologically confirmed unresectable advanced or metastatic small
cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), neuroendocrine
prostate cancer (NEPC) and gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC),
previously treated with all existing 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 NSCLC are eligible for this study, given they meet
the above criteria.
4. 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 for dose levels 1 and 2 and within 6 months for
all other dose levels (including expansion cohorts).
• Patient's tumor sample will be investigated for DLL3 expression in tumor cells as
determined by central lab immunohistochemistry (IHC) testing and compared with
emerging clinical outcome.
6. ECOG performance status of 0 or 1.
7. Adequate organ function confirmed at screening and within 96 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).
9. Negative serum pregnancy test within 72 hours before starting study treatment in all
pre-menopausal women, and women < 24 months after the onset of menopause (had a
menstrual period in past 24 months) and are of childbearing potential (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 participants and partners of study patients) during the study and until at
least 7 months after receiving the last dose of study treatment. Examples of
contraceptive methods with a failure rate of < 1% per year include bilateral tubal
ligation, male sterilization, established, proper use of hormonal contraceptives that
inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine
devices. The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, or post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
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.
5. Patients with a history of (non-infectious) pneumonitis that required steroids,
current pneumonitis, or a history of interstitial lung disease. History of COVID- 19
pneumonia with fibrotic changes.
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.
10. Prior T-cell, NK cell, 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, ≤ 5 half-lives or 3 weeks, whichever is
shorter (6 weeks for nitrosourea or mitomycin-C), targeted therapy, or immunotherapy
within 4 weeks prior to starting study drug. Concurrent use of hormone deprivation
therapy for hormone refractory prostate is permitted; participants 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 and Sponsor approval).
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 and Sponsor approval).
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, Sucrose, (PT217
inactive ingredients).
