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: 738
• 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; Platinum Resistant Ovarian Cancer; Fallopian Tube Cancer; Renal Cell Carcinoma (RCC); Papillary Renal Cell Carcinoma (Prcc); Uterine Serous Carcinoma (USC); NSCLC (Non-small Cell Lung Cancer); Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (3)

• dose escalation: Dose-limiting toxicity (DLT)

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

• dose escalation & optimization: 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 - PROC

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 PROC.

Drug: SIM0505 for injection

SIM0505 mono dose optimization - RCC

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 RCC.

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 USC.

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 NSCLC.

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:
• Participants with histologically or cytologically confirmed high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
• 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.
• 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:
• Participants with histologically- or cytologically-confirmed clear cell RCC or papillary RCC.
• 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.
• For papillary RCC: Participants without any prior systemic treatment is acceptable.

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%).
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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 within 2 weeks for focal radiation or within 4 weeks for wide-field radiation.

Sponsors & Collaborators

• NextCure, Inc.: lead
• Shanghai Simcere Zaiming Biotechnology Co., Ltd.: collaborator

Study Sites (17)

Sarah Cannon Research Institute (SCRI) - Lake Nona

Orlando, Florida, 32827, United States

ACTIVE NOT RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

ACTIVE NOT RECRUITING

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

New Orleans, Louisiana, 70112, United States

ACTIVE NOT RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

ACTIVE NOT RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

ACTIVE NOT RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10128, United States

ACTIVE NOT RECRUITING

Sarah Cannon Research Institute (SCRI) - Nashville

Nashville, Tennessee, 37203, United States

ACTIVE NOT RECRUITING

UT Health San Antonio - Mays Cancer Center

San Antonio, Texas, 78229, United States

ACTIVE NOT 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

Conditions

Fallopian Tube Neoplasms; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung

Interventions

Injections

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

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: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); CN (8)