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

NCT ID: NCT06792552

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

414 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-26

Study Completion Date

2028-08-31

Brief Summary

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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

Detailed Description

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Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

SIM0505 for injection

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

SIM0505 for injection

Intervention Type DRUG

Every 21 days is one cycle. Multiple dose levels of SIM0505 will be explored in dose escalation, and determine the maximum tolerated dose.

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.

Group Type EXPERIMENTAL

SIM0505 for injection

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

SIM0505 for injection

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

SIM0505 for injection

Intervention Type DRUG

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

Interventions

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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.

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shanghai Xianxiang Medical Technology Co., Ltd.

INDUSTRY

Sponsor Role collaborator

NextCure, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Sarah Cannon Research Institute (SCRI) - Lake Nona

Orlando, Florida, United States

Site Status RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Sarah Cannon Research Institute (SCRI) - Nashville

Nashville, Tennessee, United States

Site Status RECRUITING

UT Health San Antonio - Mays Cancer Center

San Antonio, Texas, United States

Site Status RECRUITING

The first medical center of PLA general hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

HunanCancer Hospital

Changsha, Hunan, China

Site Status RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, Shandong, China

Site Status RECRUITING

Affiliated Hospital of Jining Medical University

Jining, Shandong, China

Site Status RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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United States China

Central Contacts

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Udayan Guha, PhD, MD

Role: CONTACT

Phone: 301-919-4218

Email: [email protected]

Siyuan Qian

Role: CONTACT

Email: [email protected]

Facility Contacts

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Ingrid Acker, BSN,RN,CCRP

Role: primary

Oncology Clinical Research Referral Office

Role: primary

Kimberly Benczkowski

Role: primary

SCRI Main Email

Role: primary

Adrianna Amaya

Role: primary

Yi Hu, Ph D

Role: primary

Jundong Li

Role: primary

Dihong Tang

Role: primary

Yan Zhang

Role: primary

Xiaowei Liu

Role: primary

Xiaohua Wu, Ph D

Role: primary

Other Identifiers

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SIM0505-101

Identifier Type: -

Identifier Source: org_study_id