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

August 13, 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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
738

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100000
        • Recruiting
        • The first medical center of PLA general hospital
        • Contact:
          • Yi Hu, Ph D
    • China
      • Shenyang, China, China, 110092
        • Not yet recruiting
        • Liaoning cancer Hospital & Institute
        • Contact:
          • Hongxu Liu
      • Shijiazhuang, China, China, 050010
        • Not yet recruiting
        • The Fourth Hospital of Hebei Medical University (Heibei Tumor Hospital)
        • Contact:
          • Ziqiang Tian
        • Contact:
          • Mingxia Wang
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-Sen University Cancer Center
        • Contact:
          • Jundong Li
    • Hunan
      • Changsha, Hunan, China, 430100
        • Recruiting
        • HunanCancer Hospital
        • Contact:
          • Dihong Tang
        • Principal Investigator:
          • Shusuan JIANG
    • Shandong
      • Jinan, Shandong, China, 250117
        • Recruiting
        • Cancer Hospital of Shandong First Medical University
        • Contact:
          • Yan Zhang
      • Jining, Shandong, China, 272000
        • Recruiting
        • Affiliated Hospital of Jining Medical University
        • Contact:
          • Xiaowei Liu
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
          • Xiaohua Wu, Ph D
  • United States
    • Florida
      • Orlando, Florida, United States, 32827
        • Active, not recruiting
        • Sarah Cannon Research Institute (SCRI) - Lake Nona
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Active, not recruiting
        • Emory Winship Cancer Institute
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Active, not recruiting
        • University Medical Center of New Orleans LSU-LCMC Health Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Active, not recruiting
        • Dana-Farber Cancer Institute
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Active, not recruiting
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, United States, 14263
        • Active, not recruiting
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10128
        • Active, not recruiting
        • Icahn School of Medicine at Mount Sinai
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Active, not recruiting
        • Sarah Cannon Research Institute (SCRI) - Nashville
    • Texas
      • San Antonio, Texas, United States, 78229
        • Active, not recruiting
        • UT Health San Antonio - Mays Cancer Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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:

    1. Participants with histologically or cytologically confirmed high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
    2. Have platinum-resistant disease, defined as: participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a best response of CR or PR, and then progressed between >90 days and ≤180 days after the date of the last dose of platinum; participants who have received ≥2 lines of platinum therapy must have progressed ≤180 days after the date of the last dose of platinum.
    3. At least one line of therapy containing anti-VEGF therapy (e.g., bevacizumab or suvemcitug or their biosimilar), unless the participant is not eligible for treatment with anti- angiogenic treatment due to precautions/intolerance. Has had prior poly-ADP ribose polymerase (PARP) inhibitors for subjects with documented breast cancer gene (BRCA) mutation (germline and/or somatic), unless the subject is not eligible for treatment with a PARP inhibitor. Has had prior treatment with mirvetuximab soravtansine for participants with documented high folate receptor alpha expression, unless the subject is not eligible for treatment with mirvetuximab soravtansine due to precautions/intolerance, or if the treatment is not approved or available locally. In the PROC cohort, topoisomerase inhibitor payload ADC-pretreated participants should have received at least one prior topoisomerase inhibitor payload ADC.

    Renal cell carcinoma cohort:

    1. Participants with histologically- or cytologically-confirmed clear cell RCC or papillary RCC.
    2. For clear cell RCC: Participants who have progressed on or after systemic treatment including a programmed cell death protein 1 or programmed death ligand 1 (PD-1/PD-L1) checkpoint inhibitor and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI), either given concurrently or in separate lines of therapy.
    3. For papillary RCC: Participants without any prior systemic treatment is acceptable.

    Uterine serous carcinoma cohort:

    1. Participants with histologically- or cytologically-confirmed USC.
    2. Have progressed on or after systemic treatment that contained platinum-based chemotherapy.

    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.
    3. For participants without actionable mutations: Have progressed on or after systemic treatment including anti-PD-1/PD-L1 antibody and platinum-based chemotherapy, either given concurrently or in separate lines of therapy. Progression within 6 months after completion of adjuvant therapy is considered failure of first-line therapy.
    4. For participants with actionable mutations other than EGFR: Have failed at least one established standard anti-cancer targeted therapy, anti-PD-1/PD-L1 antibody and platinum-based chemotherapy (PD-1/PD-L1 and chemotherapy either given concurrently or in separate lines of therapy) or in the opinion of the Investigator have been considered ineligible for a particular form of standard of care therapy on medical grounds.
  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 who have sexual relations with WOCBP 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). For Part 1: At biomarker-screening (for NSCLC) or screening (for non-NSCLC) visit of a tumor lesion not previously irradiated for CDH6 testing.

For Part 2: Willing to undergo fresh tumor biopsy at biomarker-screening visit (for NSCLC) and screening visit (non-NSCLC) from a lesion that can be biopsied at an acceptable clinical risk as judged by the investigator.

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. For Part 2: Participants with primary platinum refractory ovarian cancer, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy.
  3. 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.
  4. Known untreated CNS metastases and/or leptomeningeal metastases. Participants are eligible if CNS metastases have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment). In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) for at least 2 weeks prior to the first dose of study treatment. Imaging performed within 28 days prior to the first dose of study treatment must document radiographic stability of CNS lesions and be performed after completion of any CNS-directed therapy.
  5. History of bowel obstruction within 3 months prior to the first dose of study treatment.
  6. Known psychiatric disorder or drug abuse that would interfere the study requirements.
  7. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment.
  8. Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment.
  9. 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.
  10. Prior exposure to other CDH6-targeted agents.
  11. Prior exposure to an ADC with a topoisomerase I inhibitor payload (e.g., raludotatug deruxtecan/DS-6000) for all cohorts except for the topoisomerase inhibitor payload ADC-pretreated participants in PROC cohort.
  12. Has not recovered (i.e., to CTCAE version 5.0 Grade 1 or to baseline) from previous anticancer therapy-induced AEs. Grade ≤2 AEs with no impact on participant safety are exceptions to this criterion and may qualify for the study.
  13. Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of SIM0505.
  14. Major surgery within 2 weeks of receiving the first dose of study treatment.
  15. 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 within 2 weeks for focal radiation or within 4 weeks for wide-field radiation.
  16. Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.
  17. Administration of strong or moderate CYP3A4 inhibitors or drugs with known risk of Torsades de Pointes (TdP) ≤ 7 days or 3 half-lives (whichever is longer) prior to the first dose of SIM0505.
  18. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
  19. Active hepatitis B or hepatitis C infection.
  20. Participants with clinically significant cardiovascular diseases.
  21. History of allogeneic organ transplantation or graft-versus-host disease.
  22. Known hypersensitivity to study drug or any of the excipients.
  23. Participant is pregnant or breastfeeding.
  24. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 - PROC
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 PROC.
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 - RCC
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 RCC.
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 USC.
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 NSCLC.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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 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
dose escalation & optimization: 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

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NextCure, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Shanghai Simcere Zaiming Biotechnology 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 26, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 13, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 21, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 24, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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