A Study to Evaluate the Safety,Tolerability, Pharmacokinetics and Clinical Activity of Mocertatug Rezetecan for Injection in Participants With Advanced Solid Tumors (BEHOLD-1)

Official title

A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of Mocertatug Rezetecan for Injection in Subjects With Advanced Solid Tumors

Overview

The goal of this study is to assess the safety and tolerability of Mocertatug Rezetecan . The study will also see how the levels of Mo-Rez change over time at different dose amount

Interventions

• Drug Mocertatug rezetecan
  Mocertatug rezetecan will be administered

Primary outcome measures

• Part 1: Number of participants with dose limiting toxicity (DLT) [Time frame: Up to 21 days]
• Part 2-Confirmed Objective Response Rate (ORR) assessed by investigator [Time frame: Up to approximately 28 months]

Secondary outcome measures (12)

• Part 1 and 2: Maximum observed concentration (Cmax) of Mocertatug Rezetecan and its components: conjugated antibody, total antibody, and small molecule toxin [Time frame: Up to approximately 31 months]
• Part 1 and 2: Time to reach Cmax (Tmax) of Mocertatug Rezetecan and its components: conjugated antibody, total antibody, and small molecule toxin [Time frame: Up to approximately 31 months]
• Part 1 and 2: Area under the concentration-time curve (AUC) of Mocertatug Rezetecan and its components: conjugated antibody, total antibody, and small molecule toxin [Time frame: Up to approximately 31 months]
• Part 1- Confirmed Objective Response Rate assessed by investigator [Time frame: Up to approximately 31 months]
• Part 1 and 2: Duration of response (DoR) assessed by investigator [Time frame: Up to approximately 31 months]
• Part 1 and 2: Progression-free survival (PFS) assessed by investigator [Time frame: Up to approximately 31 months]
• Part 1 and 2: Number of participants with treatment-emergent Anti-drug antibodies (ADA) / Neutralizing antibody (NAb) [Time frame: Up to approximately 31 months]
• Part 1 and 2: Titers of ADA to Mocertatug Rezetecan [Time frame: Up to approximately 31 months]
• Part 1 and 2: Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [Time frame: Up to approximately 31 months]
• Part 1 and 2: Change from baseline in body temperature (degree Celsius) [Time frame: Baseline (Day -1) and up to approximately 31 months]
• Part 1 and 2: Change from baseline in respiratory rate (breaths per minute) [Time frame: Baseline (Day -1) and up to approximately 31 months]
• Part 1 and 2: Change from baseline in pulse rate (beats per minute) [Time frame: Baseline (Day -1) and up to approximately 31 months]

Eligibility criteria

Inclusion criteria

• Males or females aged 18 years or older (≥18 years).
• Participants with pathologically confirmed advanced solid tumor (who have failed or are intolerant to standard of care.
• PROC cohort

• Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
• Must have received or are intolerant to 1 but no more than 4 lines of prior systemic therapy.
• Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy.
• Must have had prior bevacizumab , unless there is a documented contraindication or intolerance.
• Participants with known Folate receptor-α (FR-α) expressing tumors must have received mirvetuximab soravtansine if the regimen is locally available, unless there is a documented contraindication or intolerance.

Participants with known Breast cancer susceptibility gene (BRCA) mutated tumors should have received a Poly adenosine diphosphate-ribose polymerase (PARP) inhibitor if the regimen is locally available, unless there is a documented contraindication or intolerance.

• Endometrial cancer cohort

• Histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer.
• Must have received or are intolerant to 1 but no more than 4 lines of prior systemic therapy.
• Must have had prior platinum and PD(L)-1 inhibitor (in same regimen or in separate regimens), if the regimen is locally available, unless there is a documented contradiction or intolerance
• All epithelial histologies are permitted including carcinosarcoma.
• Participants have at least one target lesion as assessed per the RECIST 1.1
• Tumor tissue from a newly obtained biopsy or archival tumor tissue is required for retrospective detection of B7 homolog 4 (B7-H4) expression by IHC in central laboratory and other biomarker analysis. Tissue from a newly obtained biopsy is preferred. If a newly obtained biopsy is not feasible, archival tumor tissue within 2 years prior to the first dose of study drug is acceptable.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2 and no deterioration within 2 weeks before the first dose.
• Have a life expectancy of at least 12 weeks.

Exclusion criteria

• Have received any B7-H4-targeted therapy
• Have received any of cytotoxic chemotherapy drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 28 days prior to the first dose of study drug; or need to continue these drugs during the study.
• Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.
• Presence of pleural/abdominal effusion/ascites requiring clinical intervention; presence of pericardial effusion
• Major surgery within 28 days prior to the first dose of study treatment.
• Evidence of brain metastasis unless asymptomatic;
• Has inadequate bone marrow reserve or hepatic/renal functions .
• Mean Fridericia-corrected QT interval (QTcF) QTcF >450 msec or QTcF >480 msec for participants with bundle branch blocK;
• Evidence of current clinically significant arrhythmias or ECG abnormalities
• Left ventricular ejection fraction (LVEF) < 50%.
• Have severe, uncontrolled or active cardiovascular disorders, serious or poorly controlled hypertension, clinically significant bleeding symptoms or serious arteriovenous thromboembolic events
• Has current active pneumonitis/ILD or any history of ILD, any history of pneumonitis requiring steroids or immunomodulatory treatment within 90 days of planned randomization/enrollment or any history of drug-induced pneumonitis/ILD.Have received prior therapy with topoisomerase inhibitors or topoisomerase inhibitor Antibody-drug conjugate (ADCs)
• PROC

• Primary platinum refractory disease defined as those who have progressed on or within 12 weeks of last dose of first line platinum therapy not permitted.
• Non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma not permitted.
• Endometrial cancer a. Mesenchymal tumors of the uterus (uterine sarcomas) not permitted.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 18 centers

• GSK Investigational Site — Birmingham
• GSK Investigational Site — Fountain Valley
• GSK Investigational Site — Santa Rosa
• GSK Investigational Site — Lake Mary
• GSK Investigational Site — Orlando
• GSK Investigational Site — Fairway
• GSK Investigational Site — Boston
• GSK Investigational Site — Boston
• … and 10 more centers

Spain · 8 centers

• GSK Investigational Site — Barcelona
• GSK Investigational Site — Córdoba
• GSK Investigational Site — Girona
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Madrid
• GSK Investigational Site — Pozuelo de AlarcOn Madr

Canada · 5 centers

• GSK Investigational Site — Ottawa
• GSK Investigational Site — Toronto
• GSK Investigational Site — Toronto
• GSK Investigational Site — Montreal
• GSK Investigational Site — Montreal

Italy · 5 centers

• GSK Investigational Site — Aviano PN
• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• GSK Investigational Site — Naples
• GSK Investigational Site — Roma

Argentina · 4 centers

• GSK Investigational Site — Cipoletti Rio Negro
• GSK Investigational Site — Ciudad de Buenos Aires
• GSK Investigational Site — La Plata
• GSK Investigational Site — Rosario

South Korea · 4 centers

• GSK Investigational Site — Gyeonggi-do
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul
• GSK Investigational Site — Seoul

Brazil · 3 centers

• GSK Investigational Site — Barretos
• GSK Investigational Site — Goiânia
• GSK Investigational Site — Rio de Janeiro

Finland · 3 centers

• GSK Investigational Site — Helsinki
• GSK Investigational Site — Helsinki
• GSK Investigational Site — Tampere

France · 3 centers

• GSK Investigational Site — Lyon
• GSK Investigational Site — Saint-Herblain
• GSK Investigational Site — Villejuif

Japan · 3 centers

• GSK Investigational Site — Saitama
• GSK Investigational Site — Shizuoka
• GSK Investigational Site — Tokyo

United Kingdom · 3 centers

• GSK Investigational Site — Cambridge
• GSK Investigational Site — London
• GSK Investigational Site — London

Australia · 2 centers

• GSK Investigational Site — Blacktown
• GSK Investigational Site — Macquarie University

Sweden · 2 centers

• GSK Investigational Site — Stockholm
• GSK Investigational Site — Uppsala

Belgium · 1 center

• GSK Investigational Site — Leuven

Netherlands · 1 center

• GSK Investigational Site — Amsterdam

Identifiers

NCT: NCT06431594 · 222730 · 2024-513860-25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗