Neoplasms, Solid Tumors
Conditions
Keywords
Solid Tumors, Mocertatug rezetecan, Mo-Rez, GSK5733584, BEHOLD-1
Brief 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
Interventions
Mocertatug rezetecan will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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.
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants with dose limiting toxicity (DLT) | Up to 21 days | — |
| Part 2-Confirmed Objective Response Rate (ORR) assessed by investigator | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and 2: Maximum observed concentration (Cmax) of Mocertatug Rezetecan and its components: conjugated antibody, total antibody, and small molecule toxin | 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 | 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 | Up to approximately 31 months | — |
| Part 1- Confirmed Objective Response Rate assessed by investigator | 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 |
| Part 1 and 2: Duration of response (DoR) assessed by investigator | 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 |
| Part 1 and 2: Progression-free survival (PFS) assessed by investigator | 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). |
| Part 1 and 2: Number of participants with treatment-emergent Anti-drug antibodies (ADA) / Neutralizing antibody (NAb) | Up to approximately 31 months | — |
| Part 1 and 2: Titers of ADA to Mocertatug Rezetecan | 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) | Up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in body temperature (degree Celsius) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in respiratory rate (breaths per minute) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in pulse rate (beats per minute) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in blood pressure [millimetres of mercury (mmHg)] | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in weight [kilogram (kg)] | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in white blood cell count (cells per microliter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in hemoglobin (grams per deciliter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from Baseline in Platelet count (cells per microliter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from Baseline in Red Blood Cell Count (RBC) (million cells per microliter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from Baseline in haematocrit (Proportion of red blood cells in blood) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from Baseline in Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre) | Baseline (Day -1) and up to approximately 31 months | — |
| 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) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from Baseline in AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre) | 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 |
| Part 1 and 2: Change from baseline in Total Protein and Albumin (Grams per deciliter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in Amylase and Lipase (Units per liter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in Estimated glomerular filtration rate (eGFR) (milliliter per minute) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in Prothrombin Time (PT), Partial thromboplastin time (PTT) or Activated Partial Thromboplastin Time (aPTT) (seconds) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in liver panel parameter: International Normalized Ratio (INR) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in routine urine tests: Leukocyte esterase | Baseline (Day -1) and up to approximately 31 months | Leukocyte esterase measured as negative or positive |
| Part 1 and 2: Change from baseline in routine urine tests: Occult blood (10^9 Cells Per Liter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in routine urine tests: potential of hydrogen (pH) value | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in routine urine tests: Protein and bilirubin (Grams Per Liter) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change From Baseline in routine urine tests: Specific Gravity (Ratio) | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in CA-125 tumor marker among ovarian cancer participants [units per milliliter (U/mL)] | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in Thyroid stimulating hormone (TSH) [microunits per milliliter (µU/mL)] | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in free thyroxine (T4) [nanograms per deciliter (ng/dL)] | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in Electrocardiogram (ECG) readings [milliseconds (msec)] | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in Left ventricular ejection fraction (LVEF) [Percentage] | Baseline (Day -1) and up to approximately 31 months | — |
| Part 1 and 2: Change from baseline in Eastern Cooperative Oncology Group Performance Scale (ECOG PS) score | Baseline (Day -1) and up to approximately 31 months | ECOG PS is used for measuring how the disease impacts a patient's daily living abilities. The grades for the scale range from 0 (fully active) to 5 (dead), with increasing severity. |
| Part 2: Overall Survival (OS) | Up to approximately 31 months | OS is defined as the time interval between the date of randomization (or from the first dose of the investigational product) and the date of death due to any cause |
| Part 2-Confirmed Objective Response Rate (ORR) assessed by BICR | Up to approximately 31 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) |
| Part 2: Duration of response (DoR) assessed by BICR | 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 |
| Part 2: Progression-free survival (PFS) assessed by BICR | 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). |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Finland, France, Italy, Japan, Netherlands, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed