Evaluating SIM0505 for advanced solid tumors

A Phase I First-in-human, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0505 in Adult Participants With Advanced Solid Tumors

This study is testing a new treatment called SIM0505 to see if it is safe and effective for adults with advanced solid tumors that haven't responded to other therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 414 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: NextCure, Inc. (Industry-sponsored)
• Drugs / interventions: Radiation
• Locations: 17 sites (Orlando, Florida and 16 other locations)
• Trial ID: NCT06792552 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter phase 1 study aims to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of SIM0505 in adult participants with advanced solid tumors. Participants must have histologically or cytologically confirmed advanced solid tumors that have either failed or are ineligible for standard therapies. The study will involve two parts, with the first focusing on various advanced solid tumors and the second specifically targeting high-grade serous ovarian cancer and related conditions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced solid tumors that have progressed after standard treatments.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors who have limited alternatives.

How similar studies have performed: While this approach is being explored in this specific context, similar studies targeting advanced solid tumors have shown promise in the past.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent is obtained prior to any procedures that are not considered standard of care
2. ≥18 years of age.
3. In Part 1:

   1. Participants with histologically or cytologically confirmed advanced solid tumors, who have failed or are ineligible for standard of care therapies.
   2. Have progressed on at least one prior systematic anti-tumor regimen, and presence of at least one evaluable lesion according to RECIST Version 1.1. Measurable lesions are required in the backfill period.
   3. In the backfill period, eligible tumor types are limited to high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, USC, clear cell RCC, papillary RCC and adenocarcinoma of NSCLC without actionable mutation of epidermal growth factor receptor (EGFR). For participants with NSCLC, presence of CDH6 expression through immunohistochemical examination of tumor tissue by central laboratory is required.
4. In Part 2: Participants must have a diagnosis of specific type of metastatic or locally advanced solid tumors and have progressed on or cannot benefit from the most recent systematic anti-tumor regimen (unless otherwise specified), with presence of at least one measurable lesion according to RECIST Version 1.1.

Platinum-resistant ovarian cancer cohort:

a. Participants with histologically or cytologically confirmed high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

Renal cell carcinoma cohort:

a. Participants with histologically- or cytologically-confirmed clear cell RCC or papillary RCC.

Uterine serous carcinoma cohort:

a. Participants with histologically- or cytologically-confirmed USC.

Non-Small Cell Lung Cancer cohort:

1. Participants with histologically- or cytologically-confirmed adenocarcinoma of NSCLC without actionable mutation of EGFR.
2. Presence of CDH6 expression through immunohistochemical examination of tumor tissue.

   5\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

   6\. Life expectancy of ≥12 weeks. 7. Have adequate organ function as indicated by the laboratory values listed within the protocol.

   8\. Women of childbearing potential (WOCBP)must have a negative serum pregnancy test within 72 hours prior to the start of study treatment. WOCBP or male participants are required to use highly effective contraceptive methods , and agree to refrain from donating sperm/egg from signing of informed consent through 180 days after the last dose of study treatment.

   9\. Able to provide tumor tissue sample (archival or newly obtained core or excisional biopsy) at biomarker-screening (for NSCLC in both Part 1 and 2) or screening (for non-NSCLC in Part 1) visit of a tumor lesion not previously irradiated for CDH6 testing.

   Exclusion Criteria:
   1. For Part 2: has clear cell, mucinous or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer; mixed nonsmall cell and small cell carcinoma, or adenosquamous cell lung cancer with an adenocarcinoma component \<50% (the participant is eligible if the adenocarcinoma component is ≥50%).
   2. Any other malignancy within 2 years prior to the first dose of the study treatment except for localized cancers that are considered to have been cured and in the opinion of the Investigator present a low risk for recurrence.
   3. Participant has symptomatic central nervous system (CNS) metastases, or CNS metastases requiring CNS-directed local therapy (such as radiotherapy or surgery) or corticosteroids therapy within 2 weeks of first dose of study treatment.
   4. History of bowel obstruction within 3 months prior to the first dose of study treatment.
   5. Known psychiatric disorder or drug abuse that would interfere the study requirements.
   6. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment.
   7. Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment.
   8. History of non-infectious pneumonitis that has required a course of oral or intravenous steroids to assist with recovery, or interstitial lung disease (ILD) or severe obstructive pulmonary disease.
   9. Prior exposure to other CDH6-targeted agents or an ADC with a topoisomerase I inhibitor payload (e.g., raludotatug deruxtecan/DS-6000).

   12\. Major surgery within 2 weeks of receiving the first dose of study treatment.

   13\. Has received prior anti-cancer therapies within the following time frames prior to the first dose of study treatment; Previous cytotoxic therapy, anticancer targeted small molecules (e.g., tyrosine kinase inhibitors), hormonal agents within 2 weeks, Anti-cancer antibody or ADC within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study treatment, Chinese medicines/herbal preparations with anticancer indication taken within 2 weeks and/or Radiation therapy \<4 weeks.

   14\. Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.

   15\. Administration of below medications≤14 days prior to the first dose of SIM0505; Strong and moderate CYP3A4 inhibitors and Drugs with known risk of Torsades de Pointes (TdP).

   16\. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).

   17\. Active hepatitis B or hepatitis C infection 18. Participants with clinically significant cardiovascular diseases. 19. History of allogeneic organ transplantation or graft-versus-host disease. 20. Known hypersensitivity to study drug or any of the excipients. 21. Participant is pregnant or breastfeeding. 22. Other conditions that researchers consider inappropriate for inclusion.

Where this trial is running

Orlando, Florida and 16 other locations

• Sarah Cannon Research Institute (SCRI) - Lake Nona — Orlando, Florida, United States (Recruiting)
• Emory Winship Cancer Institute — Atlanta, Georgia, United States (Recruiting)
• University Medical Center of New Orleans LSU-LCMC Health Cancer Center — New Orleans, Louisiana, United States (Not_yet_recruiting)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• Hackensack University Medical Center — Hackensack, New Jersey, United States (Recruiting)
• Roswell Park Cancer Institute — Buffalo, New York, United States (Recruiting)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)
• Sarah Cannon Research Institute (SCRI) - Nashville — Nashville, Tennessee, United States (Recruiting)
• UT Health San Antonio - Mays Cancer Center — San Antonio, Texas, United States (Recruiting)
• The first medical center of PLA general hospital — Beijing, Beijing Municipality, China (Recruiting)
• Liaoning Cancer Hospital & Institute — Shenyang, China, China (Not_yet_recruiting)
• The Fourth Hospital of Hebei Medical University (Heibei Tumor Hospital) — Shijiazhuang, China, China (Not_yet_recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• HunanCancer Hospital — Changsha, Hunan, China (Recruiting)
• Cancer Hospital of Shandong First Medical University — Jinan, Shandong, China (Recruiting)
• Affiliated Hospital of Jining Medical University — Jining, Shandong, China (Recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Udayan Guha, PhD, MD

Conditions Advanced Solid Tumors