A Study of Risvutatug Rezetecan in Combination With Ivonescimab in Participants With Advanced Solid Tumors (EMBOLD PanTumour-103)

NCT07602855 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 3078902026-525721-20
• Study Type: interventional
• Target: 184
• Locations: 2 countries
• Sites: 4

Brief Summary

This is an early-phase clinical study investigating a new combination treatment, Risvutatug rezetecan (Ris-Rez) given with ivonescimab for adults with advanced solid cancers. The study aims to determine:

• What dose(s) of Ris-Rez given with ivonescimab is safe and what are the side effects?
• How does the body handle the drug(s)?
• What dose of Ris-Rez given with ivonescimab may work best and can improve the treatment of cancer?

Conditions

Neoplasms, Lung

Keywords

Risvutatug rezetecan; Ris-Rez; Ivonescimab; EMBOLD; Neoplasms, Lung

Outcome Measures

Primary Outcomes (11)

• Phase 1 and Phase 2 Number of participants with Adverse events (AEs), Serious Adverse Events (SAEs) and Adverse events of special interest (AESIs)

  Up to approximately 143 weeks

• Phase 1 and Phase 2: Number of participants with AEs leading to dose modifications including study intervention discontinuation

  Up to approximately 130 weeks

• Phase 2: Number of participants with AEs leading to dose modifications or study intervention discontinuation

  Up to approximately 130 weeks

• Phase 1 and Phase 2: Number of participants with changes in safety parameters

  Up to approximately 143 weeks

• Phase 1: Number of participants with Dose Limiting Toxicities (DLT)

  Up to 21 days

• Phase 1 and Phase 2: Number of participants with a change from baseline in vital signs

  Number of participants will be assessed

  Baseline (Day -1) and up to approximately 143 weeks

• Phase 1 and Phase 2: Number of participants with a change from baseline in body weight

  Number of participants will be assessed

  Baseline (Day -1) and up to approximately 143 weeks

• Phase 1 and Phase 2: Number of participants with a change from baseline in laboratory parameters (hematology, clinical chemistry and urinalysis)

  Number of participants will be assessed

  Baseline (Day -1) and up to approximately 143 weeks

• Phase 1 and Phase 2: Number of participants with a change from baseline in cardiac function [Electrocardiogram (ECG) and Echocardiogram (ECHO)]

  Number of participants will be assessed

  Baseline (Day -1) and up to approximately 143 weeks

• Phase 1 and Phase 2: Number of participants with a change from baseline in Eastern Cooperative Oncology Group (ECOG) performance status

  Number of participants will be assessed

  Baseline (Day -1) and up to approximately 143 weeks

• Phase 2:Confirmed Objective Response Rate (cORR)

  cORR is defined as the proportion of participants who have confirmed Complete Response (CR) or Partial Response (PR), assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1

  Up to approximately 143 weeks

Secondary Outcomes (12)

• Phase 1: Maximum observed plasma concentration (Cmax) of Ris-Rez, rezetecan and ivonescimab

  Up to approximately 169 weeks

• Phase 1: Time to reach maximum concentration (Tmax) of Ris-Rez, GSK5757810 and ivonescimab

  Up to approximately 169 weeks

• Phase 1: Area under the curve (AUC) of Ris-Rez, GSK5757810 and ivonescimab

  Up to approximately 169 weeks

• Phase 1: Trough concentration (Ctrough) of Ris-Rez, GSK5757810 and ivonescimab

  Up to approximately 169 weeks

• Phase 1: Confirmed Objective Response Rate (cORR)

  Up to approximately 143 weeks

Study Arms (2)

Phase 1: Dose escalation

EXPERIMENTAL

Biological: Risvutatug rezetecan; Biological: Ivonescimab

Phase 2: Dose expansion

EXPERIMENTAL

Biological: Risvutatug rezetecan; Biological: Ivonescimab

Interventions

Ivonescimab BIOLOGICAL

Ivonescimab will be administered

Phase 1: Dose escalation; Phase 2: Dose expansion

Risvutatug rezetecan BIOLOGICAL

Risvutatug rezetecan will be administered

Phase 1: Dose escalation; Phase 2: Dose expansion

Eligibility Criteria

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

You may qualify if:

• Participants are eligible to be included in the study only if all the following criteria apply:
• Male or female participants at least 18 years of age (≥18 years) at the time of signing the informed consent form (ICF).
• Participants with histologically confirmed advanced/metastatic solid tumors, irrespective of mutational status, as defined per cohort, as follows:
• ES-SCLC
• Histologically or cytologically confirmed SCLC (prior pathological diagnosis of complex SCLC \[such as mixed SCLC and NSCLC\] or transformed SCLC \[NSCLC to SCLC\] is not allowed)
• ES-SCLC \[per Veterans Administration Lung Study Group (VALG) criteria\] at study entry Squamous NSCLC or non-squamous NSCLC
• Histologically or cytologically confirmed Squamous or Non-squamous NSCLC.
• Metastatic NSCLC (Stage IV), according to American Joint Committee on Cancer (AJCC) 8th edition,
• Has at least 1 target lesion per RECIST 1.1, as determined by the investigator. Measurable lesions that have been previously irradiated and have been shown to be progressing following irradiation may be considered as TLs.
• Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
• Has a life expectancy of ≥ 3 months with ability to complete at least 4 cycles of study intervention.
• Has adequate organ function
• Is willing to use adequate contraception (contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies).
• For dose expansion only: Tumor tissue (archival tumor tissue or a fresh biopsy) is required for all participants at screening. Tissue from a newly obtained fresh biopsy is preferred. If it is not feasible to obtain a fresh biopsy at screening, archival tumor tissue, (from the most recent biopsy (within 1 year), Formalin Fixation and Paraffin Embedding FFPE) block (preferred), or freshly cut slides is acceptable. If archival tissue is unavailable and it is not medically feasible to obtain fresh tissue, the medical monitor should be informed and exemption to the tissue requirement may be granted on a case-by-case basis. Tumor tissue is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression and other biomarker analysis

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to ≤Grade 1 or to baseline status preceding prior therapy (excluding alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 1 neuropathy).
• Has had major surgical procedures or serious trauma within 4 weeks prior to first dose, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator), or minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to first dose.
• Has symptomatic Central Nervous System (CNS) metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to first dose, potential need for CNS radiation within the first cycle, or leptomeningeal disease. Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent).
• Has any of the following:
• QTc \>450 msec or QTc \>480 msec for participants with bundle branch block.
• Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval \>250 msec).
• Risk factors of prolonged QTc or arrhythmia events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of any direct relative under 40 years old or any concomitant medications that prolong the QT interval.
• Left Ventricular Ejection Fraction (LVEF) \<50%.
• Has severe, uncontrolled or active CV disorders
• Serious or poorly controlled hypertension; adjustment of antihypertensive medications due to poor blood pressure control within 2 weeks prior to the first dose; recurrent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg during screening period.
• History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to first dose, including but not limited to:
• Hemoptysis (defined as coughing up ≥ 1 teaspoon of fresh blood or small blood clots)
• Transient hemoptysis associated with diagnostic bronchoscopy is allowed.
• Nasal bleeding/epistaxis (bloody nasal discharge is allowed)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Los Angeles, California, 90027, United States

RECRUITING

GSK Investigational Site

Wilson, North Carolina, 27893-3484, United States

RECRUITING

GSK Investigational Site

Canton, Ohio, 44718, United States

RECRUITING

GSK Investigational Site

Osaka, 573-1191, Japan

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

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

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: May 22, 2026
• Study Start: September 9, 2026
• Primary Completion (Estimated): June 22, 2029
• Study Completion (Estimated): December 24, 2029
• Last Updated: September 23, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

Locations

JP (1); US (3)