A Phase 1/1b of RNDO-564 Single Agent or in Combination With Pembrolizumab in Bladder Cancer and Other Solid Tumors Associated With Nectin-4

NCT07218003 | Enrolling By Invitation Phase 1 FDA Drug

• 1 other identifier: RNDO-564-001
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 11

Brief Summary

The main goal of this study is to evaluate how safe and tolerable RNDO-564 is and to identify the best dose of RNDO-564 as a single agent and in combination with pembrolizumab. The study is focused on participants with certain solid tumors that are in an advanced stage and have certain tumor makers. This will be done by measuring the side effects that participants experience and how severe they are. Additionally, the study will evaluate how RNDO-564 moves into, through, and out of the body and how the treatment affects the body. The second goal of this study is to evaluate how well RNDO-564 works by itself or in combination with pembrolizumab at treating participants' cancer. This will be done by measuring the number of participants who respond to the treatment. The length of time where the tumor does not grow or spread will also be measured. Participants will take RNDO-564 weekly on Days 1, 8 and 15 of a 21 day cycle. Participants in the combination arms will take RNDO-564 as described with pembrolizumab every 3 weeks.

Conditions

Cervical Cancer; Head and Neck Squamous Cell Cancer; Triple Negative Breast Cancer (TNBC); Urothelial Carcinoma Bladder; Gastroesophageal Junction (GEJ) Adenocarcinoma; Esophageal Squamous Cell Cancer; Gastric Cancer; Cancer; Solid Tumors (Phase 1); Non Small Cell Lung Cancer

Keywords

RNDO-564-001; bladder cancer; bispecific antibody; solid tumors; Nectin-4; dose escalation; Phase 1/1b; CD28 x Nectin-4 bispecific; T-cell engager; CD28 costimulation

Outcome Measures

Primary Outcomes (2)

• All Arms: - Proportion of participants with adverse events (including dose limiting toxicities) as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0

  • Type, frequency, and severity of adverse events (AEs)

  From Day 1 to 90-days post last dose

• Dose Optimization Arms: • Identify one or more recommended Phase 2 doses (RP2D)

  To evaluate the totality of data

  From Day 1 up to 24 months

Secondary Outcomes (6)

• All Arms: To evaluate serum concentrations at specified timepoints of RNDO-564 as a single agent or in combination with pembrolizumab

  From Day 1 up to 25 months (inclusive of 30 day safety follow-up)

• All Arms: Proportion of participants that develop anti-drug antibodies to RNDO-564

  Baseline (predose) up to 25 months (inclusive of 30 day safety follow-up)

• All Arms: Evaluate the prevalence, incidence and impact of anti-drug antibodies to RNDO-564

  From Baseline (predose) up to 25 months (inclusive of the 30 day safety follow-up).

• All Arms: Objective Response Rate Among Participants

  percentage of participants from Day 1 until the date of the first documented partial response or complete response assessed up to 24 months

• All Arms: Duration of Response

  Time between the first partial response or complete response and the date of first documented progression or date of death, whichever came first, assessed up to 24 months

Study Arms (15)

Single Agent Dose Level 1

EXPERIMENTAL

Single Agent Dose Level 1

Drug: RNDO-564

Single Agent Dose Level 2

EXPERIMENTAL

Single Agent Dose Level 2

Drug: RNDO-564

Single Agent Dose Level 3

EXPERIMENTAL

Single Agent Dose Level 3

Drug: RNDO-564

Single Agent Dose Level 4

EXPERIMENTAL

Single Agent Dose Level 4

Drug: RNDO-564

Single Agent Dose Level 5

EXPERIMENTAL

Single Agent Dose Level 5

Drug: RNDO-564

Single Agent Dose Level 6

EXPERIMENTAL

Single Agent Dose Level 6

Drug: RNDO-564

Single Agent Dose Level 7

EXPERIMENTAL

Single Agent Dose Level 7

Drug: RNDO-564

Single Agent Dose Level 8

EXPERIMENTAL

Single Agent Dose Level 8

Drug: RNDO-564

Single Agent Dose Level 9

EXPERIMENTAL

Single Agent Dose Level 9

Drug: RNDO-564

Combination Dose Escalation- Dose Level 1

EXPERIMENTAL

Combination Dose Escalation- Dose Level 1

Drug: RNDO-564; Drug: Pembrolizumab

Combination Dose Escalation - Dose Level 2

EXPERIMENTAL

Combination Dose Escalation - Dose Level 2

Drug: RNDO-564; Drug: Pembrolizumab

Single Agent Dose Optimization - Dose Level 1

EXPERIMENTAL

Single Agent Dose Optimization - Dose Level 1

Drug: RNDO-564

Single Agent Dose Optimization - Dose Level 2

EXPERIMENTAL

Single Agent Dose Optimization - Dose Level 2

Drug: RNDO-564

Combination Dose Optimization - Dose Level 1

EXPERIMENTAL

Combination Dose Optimization - Dose Level 1

Drug: RNDO-564; Drug: Pembrolizumab

Combination Dose Optimization- Dose Level 2

EXPERIMENTAL

Combination Dose Optimization - Dose Level 2

Drug: RNDO-564; Drug: Pembrolizumab

Interventions

RNDO-564 DRUG

CD28 x Nectin-4 bispecific

Combination Dose Escalation - Dose Level 2; Combination Dose Escalation- Dose Level 1; Combination Dose Optimization - Dose Level 1; Combination Dose Optimization- Dose Level 2; Single Agent Dose Level 1; Single Agent Dose Level 2; Single Agent Dose Level 3; Single Agent Dose Level 4; Single Agent Dose Level 5; Single Agent Dose Level 6; Single Agent Dose Level 7; Single Agent Dose Level 8; Single Agent Dose Level 9; Single Agent Dose Optimization - Dose Level 1; Single Agent Dose Optimization - Dose Level 2

Pembrolizumab DRUG

Anti-PD-1 therapy

Combination Dose Escalation - Dose Level 2; Combination Dose Escalation- Dose Level 1; Combination Dose Optimization - Dose Level 1; Combination Dose Optimization- Dose Level 2

Eligibility Criteria

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

You may qualify if:

• \) Eligible tumor types: Histologic documentation of incurable, locally advanced or metastatic solid tumors for which established standard systemic therapies are no longer effective (participant must have experienced progressive disease), are not tolerated, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds or have been declined by the participant, with these tumor subtypes:
• A. Monotherapy and Combination Dose Escalation Arms:
• RR la/mUC: Participants with urothelial cancer (transitional cell) with squamous differentiation or mixed cell types are eligible. Participants with upper tract disease, e.g., involving ureters, or renal pelvis, are eligible. Participants may have had up to 2 prior monomethyl auristatin E (MMAE)-containing therapies, assuming any existing peripheral neuropathy is Grade 2 or less.
• NSCLC
• HNSCC
• GC and GEJ
• TNBC
• B. Dose Optimization (Monotherapy and Combination Arms):
• Limited to participants who have RR la/mUC,
• Participants may have had up to 2 prior MMAE-containing therapies, assuming any existing peripheral neuropathy is Grade 2 or less 2. Participants must have measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.
• \. Adequate organ function

You may not qualify if:

• For Nectin-4 targeted agents (approved or investigational)
• \> one prior Nectin-4 targeted agents
• Peripheral neuropathy \> Grade 2
• Participants with a history of, or with active, inflammatory skin disease, such as eczema, psoriasis that required or currently require biologics or oral steroids to control disease are ineligible.

Sponsors & Collaborators

• Rondo Therapeutics: lead

Study Sites (11)

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Carolina Biooncology

Huntersville, North Carolina, 28078, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Sarah Cannon Research Institute, LLD

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

START Center for Cancer Research

San Antonio, Texas, 78229, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Triple Negative Breast Neoplasms; Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Stomach Neoplasms; Neoplasms; Urinary Bladder Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Squamous Cell; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Thomas Manley, MD

  Rondo Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 14, 2025
• First Posted: October 20, 2025
• Study Start: November 17, 2025
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)