A Study of GSK5764227 in Participants With Advanced Solid Tumors (EMBOLD)

NCT06551142 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2230542024-513663-10
• Study Type: interventional
• Target: 845
• Locations: 13 countries
• Sites: 67

Brief Summary

The goal of this study is to assess the safety, tolerability, clinical activity and pharmacokinetics of Risvutatug rezetecan (Ris-Rez), also known as GSK5764227. The study will also see how the levels of Ris-Rez will change over time at different dose amounts when administered alone and in combination with other medicines like carboplatin, cisplatin, atezolizumab, pembrolizumab, durvalumab, bevacizumab, cetuximab, tarlatamab, dostarlimab

Conditions

Neoplasms

Keywords

Solid Tumors; GSK5764227; Neoplasms; EMBOLD PanTumor-101; Risvutatug rezetecan; Ris-Rez

Outcome Measures

Primary Outcomes (6)

• Phase 1a: Number of participants with Adverse Events (AEs)

  Up to approximately 28 months

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

  Up to 21 days

• Phase 1a: Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity

  Up to approximately 30 months

• Phase 1a: Number of participants with AEs leading to dose modifications

  Up to approximately 28 months

• Phase 1a: Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status

  Up to approximately 28 months

• Phase 1b: 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 version 1.1 (RECIST V1.1) criteria or other imaging criteria for defined tumor types.

  Up to approximately 27 months

Secondary Outcomes (18)

• Phase 1a and Phase 1b: Maximum concentration (Cmax) of Ris-Rez

  Up to approximately 28 months

• Phase 1a and Phase 1b: Time to reach maximum concentration (Tmax) of Ris-Rez

  Up to approximately 28 months

• Phase 1a and Phase 1b: Area under the curve (AUC) of Ris-Rez

  Up to approximately 28 months

• Phase 1a and Phase 1b: Trough concentration (Ctrough) of Ris-Rez (conjugated antibody)

  Up to approximately 28 months

• Phase 1a and Phase 1b: Trough concentration (Ctrough) of Ris-Rez (total antibody)

  Up to approximately 28 months

Study Arms (6)

Phase 1a- Dose escalation- Monotherapy

EXPERIMENTAL

Biological: Ris-Rez

Phase 1a- Dose escalation- Combination therapy

EXPERIMENTAL

Biological: Ris-Rez; Drug: Cisplatin; Drug: Carboplatin; Biological: Atezolizumab; Biological: Pembrolizumab; Biological: Durvalumab; Biological: Cetuximab; Biological: Bevacizumab; Biological: Tarlatamab; Biological: Dostarlimab

Phase 1b- Dose optimisation- Monotherapy

EXPERIMENTAL

Biological: Ris-Rez

Phase 1b- Dose optimisation- Combination therapy

EXPERIMENTAL

Biological: Ris-Rez; Biological: Atezolizumab; Biological: Dostarlimab

Phase 1b- Dose expansion- Monotherapy

EXPERIMENTAL

Biological: Ris-Rez

Phase 1b- Dose expansion- Combination therapy

EXPERIMENTAL

Biological: Ris-Rez; Biological: Tarlatamab

Interventions

Cisplatin DRUG

Cisplatin will be administered

Phase 1a- Dose escalation- Combination therapy

Carboplatin DRUG

Carboplatin will be administered

Phase 1a- Dose escalation- Combination therapy

Atezolizumab BIOLOGICAL

Atezolizumab will be administered

Phase 1a- Dose escalation- Combination therapy; Phase 1b- Dose optimisation- Combination therapy

Pembrolizumab BIOLOGICAL

Pembrolizumab will be administered

Phase 1a- Dose escalation- Combination therapy

Durvalumab BIOLOGICAL

Durvalumab will be administered

Phase 1a- Dose escalation- Combination therapy

Cetuximab BIOLOGICAL

Cetuximab will be administered

Phase 1a- Dose escalation- Combination therapy

Bevacizumab BIOLOGICAL

Bevacizumab will be administered

Phase 1a- Dose escalation- Combination therapy

Ris-Rez BIOLOGICAL

Ris-Rez will be administered

Phase 1a- Dose escalation- Combination therapy; Phase 1a- Dose escalation- Monotherapy; Phase 1b- Dose expansion- Combination therapy; Phase 1b- Dose expansion- Monotherapy; Phase 1b- Dose optimisation- Combination therapy; Phase 1b- Dose optimisation- Monotherapy

Tarlatamab BIOLOGICAL

Tarlatamab will be administered

Phase 1a- Dose escalation- Combination therapy; Phase 1b- Dose expansion- Combination therapy

Dostarlimab BIOLOGICAL

Dostarlimab will be administered

Phase 1a- Dose escalation- Combination therapy; Phase 1b- Dose optimisation- Combination therapy

Eligibility Criteria

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

You may qualify if:

• Male or female participants at least 18 years of age (≥18 years)
• Participants with histologically confirmed advanced/metastatic solid tumors, as defined per study phase and cohort, as follows:
• Phase 1a:
• Participants with advanced/metastatic solid tumors.
• For monotherapy dose escalation: participants must have progressed on or become intolerant to all available SOC therapies.
• For combination dose escalation: participants must have received 3 or fewer prior lines of systemic anticancer therapy in the advanced/metastatic setting
• Has at least 1 target lesion per RECIST 1.1, as determined by the investigator.
• Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
• Has adequate organ function.
• Where available, participants should provide a formalin fixed and paraffin embedded (FFPE) tumor sample from the most recent biopsy of primary cancer or from a metastatic site for central testing.

You may not qualify if:

• Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to ≤Grade 1 or to the baseline status preceding prior therapy.
• Prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
• Primary brain tumor or evidence of brain metastasis (unless meeting the following criteria at the same time: asymptomatic; medically stable for at least 4 weeks prior to initial dosing; no steroid treatment required for at least 4 weeks prior to initial dosing; and no midline shift due to herniation); or untreated progression due to brain metastasis or primary brain tumor during or after the last treatment prior to screening; or evidence of meningeal/brainstem involvement; or evidence of spinal cord compression (detected by radiographic examination, symptomatic or not).
• Any of the following cardiac examination abnormality:
• Has QT interval, corrected for heart rate (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 \[AV\] block, second-degree AV 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, clinically significant bleeding symptoms or serious arteriovenous thromboembolic events
• Participants with evidence of current ILD/non-infectious pneumonitis OR a prior history of ILD/non-infectious pneumonitis requiring high-dose glucocorticoids OR suspected ILD/non-infectious pneumonitis that cannot be ruled out by imaging.
• Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
• Has received prior anticancer therapy within 28 days of the first dose of study intervention or having to continue these medications during the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (67)

GSK Investigational Site

Stanford, California, 94063, United States

RECRUITING

GSK Investigational Site

Denver, Colorado, 80218, United States

RECRUITING

GSK Investigational Site

New Haven, Connecticut, 06511, United States

RECRUITING

GSK Investigational Site

Fort Wayne, Indiana, 46804, United States

RECRUITING

GSK Investigational Site

Boston, Massachusetts, 02114, United States

RECRUITING

GSK Investigational Site

Detroit, Michigan, 48201, United States

RECRUITING

GSK Investigational Site

New Brunswick, New Jersey, 08903, United States

RECRUITING

GSK Investigational Site

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

GSK Investigational Site

Nashville, Tennessee, 37203, United States

RECRUITING

GSK Investigational Site

Austin, Texas, 78705, United States

RECRUITING

GSK Investigational Site

Dallas, Texas, 75230, United States

RECRUITING

GSK Investigational Site

San Antonio, Texas, 78229, United States

RECRUITING

GSK Investigational Site

Tyler, Texas, 75702, United States

RECRUITING

GSK Investigational Site

West Valley City, Utah, 84119, United States

RECRUITING

GSK Investigational Site

Norfolk, Virginia, 23502, United States

RECRUITING

GSK Investigational Site

Rosario, S2002, Argentina

COMPLETED

GSK Investigational Site

Viedma, R8500ACE, Argentina

RECRUITING

GSK Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

GSK Investigational Site

Toronto, Ontario, M5G 1X6, Canada

RECRUITING

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

GSK Investigational Site

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

GSK Investigational Site

Bordeaux, 33076, France

RECRUITING

GSK Investigational Site

Lyon, 69373, France

RECRUITING

GSK Investigational Site

Villejuif, 94805, France

RECRUITING

GSK Investigational Site

Pokfulam, Hong Kong

RECRUITING

GSK Investigational Site

Shatin, Hong Kong

RECRUITING

GSK Investigational Site

Jerusalem, 91031, Israel

RECRUITING

GSK Investigational Site

Jerusalem, 9112001, Israel

RECRUITING

GSK Investigational Site

Ramat Gan, 5266202, Israel

RECRUITING

GSK Investigational Site

Tel Aviv, 64239, Israel

RECRUITING

GSK Investigational Site

Milan, 20141, Italy

RECRUITING

GSK Investigational Site

Naples, 80131, Italy

RECRUITING

GSK Investigational Site

Roma, 00168, Italy

RECRUITING

GSK Investigational Site

Verona, 37134, Italy

RECRUITING

GSK Investigational Site

Aichi, 464-8681, Japan

RECRUITING

GSK Investigational Site

Chiba, 277-8577, Japan

RECRUITING

GSK Investigational Site

Shizuoka, 411-8777, Japan

RECRUITING

GSK Investigational Site

Tokyo, 104-0045, Japan

RECRUITING

GSK Investigational Site

Tokyo, 135-8550, Japan

RECRUITING

GSK Investigational Site

Panama City, Panama

RECRUITING

GSK Investigational Site

Panama City, Panama

RECRUITING

GSK Investigational Site

Gyeonggi-do, 10408, South Korea

RECRUITING

GSK Investigational Site

Seoul, 03080, South Korea

RECRUITING

GSK Investigational Site

Seoul, 03722, South Korea

RECRUITING

GSK Investigational Site

Seoul, 135-710, South Korea

RECRUITING

GSK Investigational Site

Badajoz, 06080, Spain

RECRUITING

GSK Investigational Site

Barcelona, 08035, Spain

RECRUITING

GSK Investigational Site

Barcelona, 08036, Spain

RECRUITING

GSK Investigational Site

Madrid, 28034, Spain

RECRUITING

GSK Investigational Site

Madrid, 28040, Spain

RECRUITING

GSK Investigational Site

Madrid, 28041, Spain

RECRUITING

GSK Investigational Site

Málaga, 29010, Spain

RECRUITING

GSK Investigational Site

Valencia, 46026, Spain

RECRUITING

GSK Investigational Site

Zaragoza, 50009, Spain

RECRUITING

GSK Investigational Site

Changhua, 500, Taiwan

RECRUITING

GSK Investigational Site

Kaohsiung City, 83301, Taiwan

RECRUITING

GSK Investigational Site

Taichung, 40447, Taiwan

RECRUITING

GSK Investigational Site

Tainan, 704, Taiwan

RECRUITING

GSK Investigational Site

Taipei, 10002, Taiwan

RECRUITING

GSK Investigational Site

Taipei, 11217, Taiwan

RECRUITING

GSK Investigational Site

Edinburgh, EH4 2XU, United Kingdom

RECRUITING

GSK Investigational Site

Glasgow, G12 0YN, United Kingdom

RECRUITING

GSK Investigational Site

London, W1G 6AD, United Kingdom

RECRUITING

GSK Investigational Site

London, WC1E 6AG, United Kingdom

RECRUITING

GSK Investigational Site

Manchester, M20 4BX, United Kingdom

RECRUITING

GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

Cisplatin; Carboplatin; atezolizumab; pembrolizumab; durvalumab; Cetuximab; Bevacizumab; dostarlimab

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2024
• First Posted: August 13, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): October 16, 2028
• Study Completion (Estimated): June 8, 2029
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); PA (2); TW (6); US (15); FR (3); AR (2); GB (6); JP (5); KR (4); ES (9); CA (5); HK (2); IL (4)