Clinical Trial · NCT06941480

Characterizing the Theranostic Potential of DLL3-targeting Agents in High-grade Neuroendocrine Carcinomas of the Lung and Prostate

Overview

The purpose of this study is to find out whether 177Lu-DTPA-SC16.56 is a safe treatment for people with small-cell lung cancer or neuroendocrine prostate cancer

Sponsor

Memorial Sloan Kettering Cancer Center

Phase

Phase 1

ClinicalTrials.gov

NCT06941480

Study contact

Michael Morris, MD

morrism@mskcc.org 646-422-4471

Lisa Bodei, MD, PhD

bodeil@mskcc.org 212-639-7373

Drug / Compound

177Lu-DTPA-SC16.56

Isotope(s):

Target(s):

DLL3

Eligibility

Inclusion

In order to proceed with the treatment with 177Lu-DTPA-SC16.56, patients must exhibit overexpression of DLL3, as SUVmax greater than in normal liver, in ≥80% of tumor lesions among the growing progressing lesions that are ≥2cm.
Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
At least one tumor lesion on CT or MR ≥ 2 cm
Previous chemotherapy, immunotherapy, and/or investigational agents are allowed if completed ≥4 weeks prior to study entry. For patients who received systemic therapy prior to study entry, there must be documented progression of measurable disease since receiving systemic therapy prior to study entry.
Preserved renal function: i. Serum creatinine ≤1.7 mg/dL ii. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2
Preserved hematological function: i. Hb ≥9.0 g/dL; ii. WBC ≥3000/mm3; iii. ANC≥1500/mm3; iv. Platelets ≥75.000/mm3
ECOG performance status 0 to 2
Preserved hepatic function: i. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN) or ≤ 5 x ULN if liver metastases are present ii. bilirubin ≤ 1.5 x ULN (unless considered due to Gilbert's syndrome or hemolysis)
Subjects with histologically proven progressive metastatic high-grade neuroendocrine carcinomas of the lung (small-cell lung cancer) and prostate (neuroendocrine prostate cancer) that has relapsed following at least 1 line of standard chemotherapy i. Prostate cancer patients will be defined by either of the following criteria: ii. The presence of chromogranin staining on tissue iii. At least two of the pathogenic mutations of PTEN, RB1, or p53 iv. Disease exclusively involving the viscera v. Disease in which the PSA is \<10 but the number of bone lesions is \>20 vi. Histologic evidence of small cell carcinoma or other stains consistent with neuroendocrine disease (on the primary disease or metastases) vii. DLL3 positivity on previously available tissue specimens
Willingness to undergo baseline and follow up biopsy to obtain tissue for DLL3 IHC and genomic analyses

Exclusion

Unmanageable urinary incontinence rendering the administration of 177Lu-DTPA-SC16.56 unsafe (e.g., urinary catheterization not feasible).
Life expectancy \< 6 months as assessed by the treating physician.
Males and females of reproductive potential who are unwilling to practice a highly effective method(s) of birth control while on study through 4 months for males and 7 months for females after receiving the therapeutic study drug. Acceptable methods of highly effective birth control include sexual abstinence (males, females); vasectomy; bilateral tubal ligation/occlusion; or a condom with spermicide (men) in combination with hormonal birth control or intrauterine device (IUD) (women)
Subjects likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge.
Prior treatment with Rova-T (rovalpituzumab)
Women who are pregnant or unwilling to discontinue breastfeeding
Concurrent chemotherapy, other radiopharmaceuticals of any type, and immunotherapy are excluded
Major surgery within 28 days of enrolment with the exception of biopsy and insertion of central venous catheter.
Spinal cord compression or symptomatic/uncontrolled epidural disease, unless treated and stable for at least 1 week prior to enrolment.
Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
History of anaphylactic reaction to humanized or human antibodies
Patients for whom their clinicians believe would benefit by continuing their treatments for their disease to control any adenocarcinoma (such as ADT or other AR axis directed therapy) can and should remain on those treatments while on this protocol, if their clinician believes that it would be clinically beneficial to do so.
Complementary approaches known to modulate PSA should not be taken while on this trial
Prostate cancer patients with mixed histologies (i.e., neuroendocrine and adenocarcinomas) are eligible provided that they meet all of the above eligibility criteria.
Unresolved toxicities from prior antitumor therapy, defined per Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, to to grade 1 or grade 0 or to levels dictated in the inclusion criteria.
History of severe allergic reaction to X-ray contrast medium despite premedication