Iadademstat in Combination With Paclitaxel in Relapsed/Refractory SCLC and Extrapulmonary High Grade NET

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed metastatic orunresectable, extrapulmonary G3 NEC (Ki-67 index > 20% with poorly-differentiatedhistology), SCLC, or prostate or bladder cancer with high-grade neuroendocrine orsmall 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 oftreatment in the metastatic setting that might include immune checkpoint inhibitors,but no previous taxane based therapy. However, patients who have receivedneoadjuvant/adjuvant therapy with taxanes more than six months from enrollment areallowed to participate.

3. Patients must have measurable disease, defined as at least one lesion that can beaccurately 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 toenroll 5 Age > 18 years. 6 ECOG performance status 0-1 7 Body weight >/= 50 kg (110lbs) 8 Patients must have normal organ and marrow function as defined below

• Absolute neutrophil count > 1,500/mcL

• Hemoglobin > 9 mg/dl

• Platelets > 100,000/mcL (patients cannot receive platelet transfusions to meeteligibility criteria)

• Total bilirubin < 1.5 X ULN (Pts with Gilbert's can enroll if conjugatedbilirubin 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 administeredstudy treatment. 10 Patients with treated brain metastases are eligible if there is no evidenceof progression for at least 4 weeks after CNS-directed treatment, asascertained by clinical examination and brain imaging (MRI or CT) during thescreening period. 11 Ability to understand and willingness to sign a written informed consent andHIPAA consent document. 12 HIV-infected patients who are healthy and have a low risk of AIDS-relatedoutcomes are included in this trial. Similarly, Hepatitis B and C infectedpatients are allowed if disease is controlled (testing not required foreligibility 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 duringthe entire study treatment period and through 180 days after the last doseof study drug.
2. Not to donate sperm during the course of this study or within 180 daysafter 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 toconsenting), OR c. If they are of childbearing potential, agree to: i. use oftwo methods of contraception (e.g., one barrier method [condom, diaphragm orcervical/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 theneoadjuvant/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 treatmenthas the potential to interfere with the safety or efficacy assessment of theinvestigational regimen as per treating MD

6. Patients who have received radiotherapy less than 2 weeks prior to first dose ofstudy medication.

7. Surgical procedure or clinically significant trauma within 4 weeks of first dose ofstudy treatment.

8. Treatment with any investigational agent ≤ 3 weeks prior to first dose of studytreatment.

9. Patients with gastrectomy or pre-existing gastrointestinal (GI) disorders that mayinterfere with the proper absorption of the drug(s), as per conclusion of theclinical Investigator.

10. Patients medicated with, or the expected need for treatment with agents reported tohave LSD1 inhibitory activity (such as tranylcypromine or phenelzine) within 3 weeksof treatment start also refer to section 5.2 for the list of concomitantmedications.

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 nervoussystem (CNS) toxicity.

13. Patients with untreated, symptomatic CNS metastases likely to interfere with theexperimental 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 otherconditions that could affect their participation in the study or pose a higher riskof toxicities as per discretion of the treating physician in agreement with theinvestigator-sponsor (including but not limited to:)

16. Unstable angina, symptomatic or otherwise uncontrolled arrhythmia (does notinclude stable, lone atrial fibrillation), QTcF > 480 ms based on the averageof 3 screening electrocardiograms (ECGs), symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first studytreatment, cerebrovascular accidents ≤ 6 months before study treatment start.

17. Patient has evidence of active uncontrolled viral, bacterial, or systemicfungal infection.

18. Any other serious and uncontrolled medical illnesses, uncontrolled seizuresthat may affect study participation or patient safety, as assessed byinvestigator.

19. Patients who refuse or are unable to potentially receive blood products

20. Any medical condition which, in the opinion of the Investigator, places the patientat an unacceptable risk for toxicities if entered into the clinical study.

21. Patients with history of clinically significant bleeding, specifically any historyof intracranial hemorrhage / hemorrhagic cardiovascular accident (CVA), or patientswith gastrointestinal bleeding within the 3 months prior to study entry.

22. Patients with current interstitial lung disease, requiring systemic therapy withinthe last 3 months.

23. Patients with hypersensitivity to iadademstat, paclitaxel, or to any of itsexcipients.

24. Patients with known irreversible bleeding disorders or receiving antiplatelettherapy for other indications. Use of low dose aspirin (<100 mg) is allowed.

25. Patients pregnant or breast feeding. Refer to section 4.4 for further detail. Femalepatient must agree not to breastfeed at screening and throughout the study periodand for 60 days after the final study drug administration.