A Phase I Study of SIM0505 in Participants With Advanced Solid Tumors

January 28, 2026 updated by: NextCure, Inc.

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 is an open-label, multicenter phase 1 study to evaluate the safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0505 in Adult Participants with Advanced Solid Tumors

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

414

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100000
        • Recruiting
        • The First Medical Center of PLA General Hospital
        • Contact:
    • China
      • Shenyang, China, China, 110092
        • Not yet recruiting
        • Liaoning cancer Hospital & Institute
        • Contact:
      • Shijiazhuang, China, China, 050010
        • Not yet recruiting
        • The Fourth Hospital of Hebei Medical University (Heibei Tumor Hospital)
        • Contact:
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun yat-sen University Cancer Center
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 430100
        • Recruiting
        • HunanCancer Hospital
        • Principal Investigator:
          • Shusuan Jiang
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250117
        • Recruiting
        • Cancer Hospital of Shandong First Medical University
        • Contact:
      • Jining, Shandong, China, 272000
        • Recruiting
        • Affiliated Hospital of Jining Medical University
        • Contact:
          • Xiaowei Liu
          • Phone Number: +86 18678766867
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
  • United States
    • Florida
      • Orlando, Florida, United States, 32827
        • Recruiting
        • Sarah Cannon Research Institute (SCRI) - Lake Nona
        • Principal Investigator:
          • Cesar Perez Batista, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory Winship Cancer Institute
        • Principal Investigator:
          • Beryl Manning-Geist, MD
        • Contact:
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Not yet recruiting
        • University Medical Center of New Orleans LSU-LCMC Health Cancer Center
        • Principal Investigator:
          • Shou-Ching Tang, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Joyce Liu, MD
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Contact:
        • Principal Investigator:
          • Miguel GonzalezVelez, MD
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Principal Investigator:
          • Emese Zsiros, MD
        • Contact:
      • New York, New York, United States, 10128
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
        • Principal Investigator:
          • Dmitriy Zamarin, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute (SCRI) - Nashville
        • Principal Investigator:
          • Erika Hamilton, MD
        • Contact:
    • Texas
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • UT Health San Antonio - Mays Cancer Center
        • Principal Investigator:
          • Daruka Mahadevan, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SIM0505 mono dose escalation
Every 21 days is one cycle. Multiple dose levels of SIM0505 will be explored in dose escalation, and determine the maximum tolerated dose.
Drug: SIM0505 for injection
Every 21 days is one cycle. Multiple dose levels of SIM0505 will be explored in dose escalation, and determine the maximum tolerated dose.
Drug: SIM0505 for injection
Every 21 days is one cycle. 2-3 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505
Experimental: SIM0505 mono dose optimization - Ovarian
Every 21 days is one cycle. 2-3 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505 in ovarian cancer.
Drug: SIM0505 for injection
Every 21 days is one cycle. Multiple dose levels of SIM0505 will be explored in dose escalation, and determine the maximum tolerated dose.
Drug: SIM0505 for injection
Every 21 days is one cycle. 2-3 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505
Experimental: SIM0505 mono dose optimization - Renal
Every 21 days is one cycle. 2 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505 in renal cancer.
Drug: SIM0505 for injection
Every 21 days is one cycle. Multiple dose levels of SIM0505 will be explored in dose escalation, and determine the maximum tolerated dose.
Drug: SIM0505 for injection
Every 21 days is one cycle. 2-3 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505
Experimental: SIM0505 mono dose optimization - USC
Every 21 days is one cycle. 2 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505 in uterine cancer.
Drug: SIM0505 for injection
Every 21 days is one cycle. Multiple dose levels of SIM0505 will be explored in dose escalation, and determine the maximum tolerated dose.
Drug: SIM0505 for injection
Every 21 days is one cycle. 2-3 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505
Experimental: SIM0505 mono dose optimization - NSCLC
Every 21 days is one cycle. 2 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505 in lung cancer.
Drug: SIM0505 for injection
Every 21 days is one cycle. Multiple dose levels of SIM0505 will be explored in dose escalation, and determine the maximum tolerated dose.
Drug: SIM0505 for injection
Every 21 days is one cycle. 2-3 dose levels of SIM0505 will be explored in dose optimization, and determine the recommended dose (RD) of SIM0505 and evaluate the preliminary anti-tumor activity of SIM0505

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
dose escalation: Dose-limiting toxicity (DLT)
Time Frame: At the end of Cycle 1 (each cycle is 21 days)
At the end of Cycle 1 (each cycle is 21 days)
dose escalation: Adverse events (AEs)
Time Frame: the whole dose escalation phase，an average of 2 year
the whole dose escalation phase，an average of 2 year
dose optimization：Objective response rate (ORR)
Time Frame: the whole dose optimization phase，an average of 1.5 year
the whole dose optimization phase，an average of 1.5 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NextCure, Inc.

Collaborators

Shanghai Xianxiang Medical Technology Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 26, 2025

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

August 1, 2028

Study Registration Dates

First Submitted

January 13, 2025

First Submitted That Met QC Criteria

January 21, 2025

First Posted (Actual)

January 24, 2025

Study Record Updates

Last Update Posted (Actual)

January 29, 2026

Last Update Submitted That Met QC Criteria

January 28, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SIM0505-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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