Inclusion Criteria:
1. Patients must have histologically or cytologically confirmed metastatic or
unresectable, extrapulmonary G3 NEC (Ki-67 index > 20% with poorly-differentiated
histology), SCLC, or prostate or bladder cancer with high-grade neuroendocrine or
small cell component. 2. Patients must have been previously treated with platinum-based chemotherapy regimens
(cisplatin, carboplatin or oxaliplatin). Patients may have received up to 3 lines of
treatment in the metastatic setting that might include immune checkpoint inhibitors,
but no previous taxane based therapy. However, patients who have received
neoadjuvant/adjuvant therapy with taxanes more than six months from enrollment are
allowed to participate.
3. Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension in accordance with RECIST criteria v.
1.1 as described in detail in section 11.0. 4. Patients who have received prior anti-PD1 or anti-PD-L1 therapy are eligible to enroll
5 Age > 18 years. 6 ECOG performance status 0-1 7 Body weight >/= 50 kg (110 lbs) 8
Patients must have normal organ and marrow function as defined below.
- - Absolute neutrophil count > 1,500/mcL.
- - Platelets > 100,000/mcL (patients cannot receive platelet transfusions to meet
eligibility criteria)
- Total bilirubin < 1.5 X ULN (Pts with Gilbert's can enroll if conjugated
bilirubin is within normal limits)
- AST/ALT (SGOT/SGPT) < 3 x ULN if not disease related.
If liver metastasis,
AST/ALT up to 5 x ULN allowed.
- - Creatinine <1.5 X ULN OR.
- - Creatinine clearance > 60 ml/min/1.73 m2 for patients.
9 Patient is able to swallow oral medications and retain orally administered
study treatment.
10 Patients with treated brain metastases are eligible if there is no evidence of
progression for at least 4 weeks after CNS-directed treatment, as ascertained by
clinical examination and brain imaging (MRI or CT) during the screening period.
11 Ability to understand and willingness to sign a written informed consent and
HIPAA consent document.
12 HIV-infected patients who are healthy and have a low risk of AIDS-related
outcomes are included in this trial. Similarly, Hepatitis B and C infected
patients are allowed if disease is controlled (testing not required for
eligibility assessment) 13 Male patients even if surgically sterilized (i.e.,
status post-vasectomy) who agree to:
1. Practice true abstinence or highly effective barrier contraception during
the entire study treatment period and through 180 days after the last dose
of study drug.
2. Not to donate sperm during the course of this study or within 180 days after
receiving their last dose of study drug.
14 Female patients who:
a. Are postmenopausal for at least 1 year before the initial consent is signed,
OR b. Are documented as surgically sterile (at least 1 month prior to
consenting), OR c. If they are of childbearing potential, agree to: i. use of two
methods of contraception (e.g., one barrier method [condom, diaphragm or
cervical/vault caps] with spermicide and one hormonal contraceptive [e.g.,
combined oral contraceptives, patch, vaginal ring, injectable and implants])
during the trial and 180 days after the end of treatment.
ii. practice true abstinence during the trial and 180 days after the end of treatment.
iii. have a negative urine pregnancy test at screening iv. not to donate or freeze egg(s)
during the course of this study or within 180 days after receiving their last dose of study
drug.
Exclusion Criteria:
1. Patients who have received more than 3 lines of therapy. 2. Patients who have not received any platinum-based therapy. 3. Patients who have received previous therapy with taxanes, unless received in the
neoadjuvant/adjuvant setting and longer than six months from last taxane treatment.
4. ECOG performance status >/=2. 5. Patients with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen as per treating MD. 6. Patients who have received radiotherapy less than 2 weeks prior to first dose of study
medication.
7. Surgical procedure or clinically significant trauma within 4 weeks of first dose of
study treatment.
8. Treatment with any investigational agent ≤ 3 weeks prior to first dose of study
treatment.
9. Patients with gastrectomy or pre-existing gastrointestinal (GI) disorders that may
interfere with the proper absorption of the drug(s), as per conclusion of the clinical
Investigator.
10. Patients medicated with, or the expected need for treatment with agents reported to
have LSD1 inhibitory activity (such as tranylcypromine or phenelzine) within 3 weeks
of treatment start also refer to section 5.2 for the list of concomitant medications.
11. History of allergic reactions attributed to components of the formulated product(s).
(see appendix)
12. Patients with prior history of NCI CTCAE Grade ≥ 3 drug-related central nervous system
(CNS) toxicity.
13. Patients with untreated, symptomatic CNS metastases likely to interfere with the
experimental therapy as per the investigator-sponsor. 14. Patients with prior history of grade ≥2 neurotoxicity that was not resolved to grade
≤1 (prior therapy toxicity)
15. Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study or pose a higher risk of
toxicities as per discretion of the treating physician in agreement with the
investigator-sponsor (including but not limited to:)
1. Unstable angina, symptomatic or otherwise uncontrolled arrhythmia (does not
include stable, lone atrial fibrillation), QTcF > 480 ms based on the average of
3 screening electrocardiograms (ECGs), symptomatic congestive heart failure (NYHA
II, III, IV), myocardial infarction ≤ 6 months prior to first study treatment,
cerebrovascular accidents ≤ 6 months before study treatment start.
2. Patient has evidence of active uncontrolled viral, bacterial, or systemic fungal
infection.
3. Any other serious and uncontrolled medical illnesses, uncontrolled seizures that
may affect study participation or patient safety, as assessed by investigator.
16. Patients who refuse or are unable to potentially receive blood products. 17. Any medical condition which, in the opinion of the Investigator, places the patient at
an unacceptable risk for toxicities if entered into the clinical study.
18. Patients with history of clinically significant bleeding, specifically any history of
intracranial hemorrhage / hemorrhagic cardiovascular accident (CVA), or patients with
gastrointestinal bleeding within the 3 months prior to study entry.
19. Patients with current interstitial lung disease, requiring systemic therapy within the
last 3 months.
20. Patients with hypersensitivity to iadademstat, paclitaxel, or to any of its
excipients.
21. Patients with known irreversible bleeding disorders or receiving antiplatelet therapy
for other indications. Use of low dose aspirin (<100 mg) is allowed.
22. Patients pregnant or breast feeding. Refer to section 4.4 for further detail. Female
patient must agree not to breastfeed at screening and throughout the study period and
for 60 days after the final study drug administration.
