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

NCT06431594
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
675
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Lead sponsor
GlaxoSmithKline
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Start date
2024-07-02
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Number of sites
65
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Summary
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
clinicaltrials.gov
Short title
A Study to Evaluate the Safety,Tolerability, Pharmacokinetics and Clinical Activity of Mocertatug Rezetecan for Injection in Participants With Advanced Solid Tumors (BEHOLD-1)
clinicaltrials.gov
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
clinicaltrials.gov

Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2029-12-31
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First posted
2024-05-28
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Registry last updated
2026-06-25
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Primary completion date
2027-09-22
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Start date
2024-07-02
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Participants
675
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Participant count basis
Estimated
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Planned participants
675
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Protocol amendments
6
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Number of sites
65
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
GlaxoSmithKline
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06431594
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ClinicalTrials.gov ID
NCT06431594
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Registry record
Open registry record
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Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Part 1: Number of participants with dose limiting toxicity (DLT)

    Timeframe: Up to 21 days

  2. Part 2-Confirmed Objective Response Rate (ORR) assessed by investigator

    Timeframe: Up to approximately 28 months

    ORR is defined as the proportion of participants with at least one confirmed Complete Response (CR) or Partial Response (PR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  1. Part 1 and 2: Maximum observed concentration (Cmax) of Mocertatug Rezetecan and its components: conjugated antibody, total antibody, and small molecule toxin

    Timeframe: Up to approximately 31 months

  2. Part 1 and 2: Time to reach Cmax (Tmax) of Mocertatug Rezetecan and its components: conjugated antibody, total antibody, and small molecule toxin

    Timeframe: Up to approximately 31 months

  3. 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

    Timeframe: Up to approximately 31 months

  4. Part 1- Confirmed Objective Response Rate assessed by investigator

    Timeframe: Up to approximately 31 months

    ORR is defined as the proportion of participants with at least one confirmed CR or PR as defined by RECIST 1.1

  5. Part 1 and 2: Duration of response (DoR) assessed by investigator

    Timeframe: Up to approximately 31 months

    DoR is defined as the time interval between the date of the first documented response (CR or PR) and the date of the first documented disease progression or death due to any cause

  6. Part 1 and 2: Progression-free survival (PFS) assessed by investigator

    Timeframe: Up to approximately 31 months

    PFS is defined as the time interval between randomization (or from the first dose of the intervention) and the first documented disease progression or death due to any cause (whichever occurs first).

  7. Part 1 and 2: Number of participants with treatment-emergent Anti-drug antibodies (ADA) / Neutralizing antibody (NAb)

    Timeframe: Up to approximately 31 months

  8. Part 1 and 2: Titers of ADA to Mocertatug Rezetecan

    Timeframe: Up to approximately 31 months

  9. Part 1 and 2: Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

    Timeframe: Up to approximately 31 months

  10. Part 1 and 2: Change from baseline in body temperature (degree Celsius)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  11. Part 1 and 2: Change from baseline in respiratory rate (breaths per minute)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  12. Part 1 and 2: Change from baseline in pulse rate (beats per minute)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  13. Part 1 and 2: Change from baseline in blood pressure [millimetres of mercury (mmHg)]

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  14. Part 1 and 2: Change from baseline in weight [kilogram (kg)]

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  15. Part 1 and 2: Change from baseline in white blood cell count (cells per microliter)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  16. Part 1 and 2: Change from baseline in hemoglobin (grams per deciliter)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  17. Part 1 and 2: Change from Baseline in Platelet count (cells per microliter)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  18. Part 1 and 2: Change from Baseline in Red Blood Cell Count (RBC) (million cells per microliter)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  19. Part 1 and 2: Change from Baseline in haematocrit (Proportion of red blood cells in blood)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  20. Part 1 and 2: Change from Baseline in Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  21. Part 1 and 2: Change from Baseline in Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium Direct Bilirubin and Total Bilirubin (milligrams per decilitre)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  22. Part 1 and 2: Change from Baseline in AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

    Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analysed

  23. Part 1 and 2: Change from baseline in Total Protein and Albumin (Grams per deciliter)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  24. Part 1 and 2: Change from baseline in Amylase and Lipase (Units per liter)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

  25. Part 1 and 2: Change from baseline in Estimated glomerular filtration rate (eGFR) (milliliter per minute)

    Timeframe: Baseline (Day -1) and up to approximately 31 months

And 17 more, listed on the interactive page.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

    1. Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
    2. Must have received or are intolerant to 1 but no more than 4 lines of prior systemic therapy.
    3. Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy.
    4. Must have had prior bevacizumab , unless there is a documented contraindication or intolerance.
    5. 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

    1. Histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer.
    2. Must have received or are intolerant to 1 but no more than 4 lines of prior systemic therapy.
    3. 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
    4. 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.

  • 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

    1. 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.
    2. 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.

Sources for eligibility
clinicaltrials.gov

  • GSK Investigational SiteBirmingham, United StatesRecruiting
  • GSK Investigational SiteFountain Valley, United StatesRecruiting
  • GSK Investigational SiteSanta Rosa, United StatesRecruiting
  • GSK Investigational SiteLake Mary, United StatesCompleted
  • GSK Investigational SiteOrlando, United StatesRecruiting
  • GSK Investigational SiteFairway, United StatesRecruiting
  • GSK Investigational SiteBoston, United StatesRecruiting
  • GSK Investigational SiteBoston, United StatesRecruiting
  • GSK Investigational SiteDetroit, United StatesRecruiting
  • GSK Investigational SiteGrand Rapids, United StatesRecruiting
  • GSK Investigational SiteMinneapolis, United StatesRecruiting
  • GSK Investigational SiteMineola, United StatesRecruiting
  • GSK Investigational SiteNew York, United StatesRecruiting
  • GSK Investigational SitePortland, United StatesRecruiting
  • GSK Investigational SiteNashville, United StatesRecruiting
  • GSK Investigational SiteDallas, United StatesRecruiting
  • GSK Investigational SiteWest Valley City, United StatesRecruiting
  • GSK Investigational SiteSeattle, United StatesRecruiting
  • GSK Investigational SiteCipoletti Rio Negro, ArgentinaRecruiting
  • GSK Investigational SiteCiudad de Buenos Aires, ArgentinaRecruiting
  • GSK Investigational SiteLa Plata, ArgentinaRecruiting
  • GSK Investigational SiteRosario, ArgentinaRecruiting
  • GSK Investigational SiteBlacktown, AustraliaRecruiting
  • GSK Investigational SiteMacquarie University, AustraliaRecruiting
  • GSK Investigational SiteLeuven, BelgiumRecruiting

And 40 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-513860-25
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (1)