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

NCT06792552 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SIM0505-101
• Study Type: interventional
• Target: 414
• Locations: 2 countries
• Sites: 17

Brief Summary

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

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• dose escalation: Dose-limiting toxicity (DLT)

  At the end of Cycle 1 (each cycle is 21 days)

• dose escalation: Adverse events (AEs)

  the whole dose escalation phase，an average of 2 year

• dose optimization：Objective response rate (ORR)

  the whole dose optimization phase，an average of 1.5 year

Study Arms (5)

SIM0505 mono dose escalation

EXPERIMENTAL

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

SIM0505 mono dose optimization - Ovarian

EXPERIMENTAL

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

SIM0505 mono dose optimization - Renal

EXPERIMENTAL

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

SIM0505 mono dose optimization - USC

EXPERIMENTAL

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

SIM0505 mono dose optimization - NSCLC

EXPERIMENTAL

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

Interventions

SIM0505 for injection 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 escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent is obtained prior to any procedures that are not considered standard of care
• ≥18 years of age.
• In Part 1:
• Participants with histologically or cytologically confirmed advanced solid tumors, who have failed or are ineligible for standard of care therapies.
• 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.
• 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.
• 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:
• Participants with histologically- or cytologically-confirmed adenocarcinoma of NSCLC without actionable mutation of EGFR.

You may not qualify if:

• 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%).
• 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.
• 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.
• History of bowel obstruction within 3 months prior to the first dose of study treatment.
• Known psychiatric disorder or drug abuse that would interfere the study requirements.
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment.
• Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment.
• 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.
• Prior exposure to other CDH6-targeted agents or an ADC with a topoisomerase I inhibitor payload (e.g., raludotatug deruxtecan/DS-6000).
• \. Major surgery within 2 weeks of receiving the first dose of study treatment.
• \. 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.
• \. Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.
• \. 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).
• \. Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).

Sponsors & Collaborators

• NextCure, Inc.: lead
• Shanghai Xianxiang Medical Technology Co., Ltd.: collaborator

Study Sites (17)

Sarah Cannon Research Institute (SCRI) - Lake Nona

Orlando, Florida, 32827, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

University Medical Center of New Orleans LSU-LCMC Health Cancer Center

New Orleans, Louisiana, 70112, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10128, United States

RECRUITING

Sarah Cannon Research Institute (SCRI) - Nashville

Nashville, Tennessee, 37203, United States

RECRUITING

UT Health San Antonio - Mays Cancer Center

San Antonio, Texas, 78229, United States

RECRUITING

The first medical center of PLA general hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, China, 110092, China

NOT YET RECRUITING

The Fourth Hospital of Hebei Medical University (Heibei Tumor Hospital)

Shijiazhuang, China, 050010, China

NOT YET RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

HunanCancer Hospital

Changsha, Hunan, 430100, China

RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, Shandong, 250117, China

RECRUITING

Affiliated Hospital of Jining Medical University

Jining, Shandong, 272000, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Udayan Guha, PhD, MD

CONTACT

301-919-4218; NCClin@nextcure.com

Siyuan Qian

CONTACT

Siyuan.Qian@zaiming.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: January 24, 2025
• Study Start: February 26, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); CN (8)