Untreated Locally Advanced Unresectable or Metastatic Renal Cell Carcinoma MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10073251 Term: Clear cell renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 25.0 Level:
Conditions
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Age >= 18 years ? Ability to comply with the protocol and provide written informed consent ? Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 ? International Metastatic Renal Cell Carcinoma Database Consortium IMDC risk intermediate (score of 1 or 2), or poor (score of 3 to 6) ? Measurable disease, at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 ? Adequate hematologic and end-organ function (within 14 days prior to study treatment) ? Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment ? Histologically confirmed clear-cell renal cell carcinoma renal cell carcinoma (ccRCC) with or without sarcomatoid features; non-clear-cell renal cell carcinoma (nccRCC) subtypes (papillary, chromophobe, and unclassified) are not allowed. ? Archival tissues will be collected from all participants for exploratory biomarker research ? Negative HIV testing at screening ? Negative hepatitis B surface antigen (HBsAg) test at screening ? Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening ? Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening ? For female participants of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 90 days after the final dose of tiragolumab for 4 months after the final dose of tobemstomig and pembrolizumab, or for 1 week after the final dose of axitinib, whichever occurs last ? For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm during the treatment period, for 4 months after the last dose of tobemstomig and pembrolizumab, for 90 days after the last dose of tiragolumab and 1 week after the last dose of axitinib whichever occurs last to avoid exposing the embryo ? For participants enrolled in the extended China enrollment phase at China's sites: must be current residents of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 93 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 117
Exclusion criteria
Exclusion criteria: ? Inability to swallow tablet or malabsorption syndrome ? Prior treatment for localized and/or metastatic RCC with systemic RCC directed therapy ? Ongoing use or anticipated need for treatment with a strong CYP3A4/5 inhibitor or inducer ? Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study ? Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab ? Participants who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible ? Symptomatic, untreated, or actively progressing CNS metastases ? Asymptomatic patients with treated CNS lesions are eligible ? History of leptomeningeal disease ? Uncontrolled tumor-related pain ? Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrollment. ? Asymptomatic metastatic lesions that would likely cause functional deficit or intractable pain with further growth should be considered for loco-regional therapy if appropriate prior to enrollment. ? Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures ? Participants with indwelling catheters are allowed ? Moderate to severe hepatic impairment (Child-Pugh B or C) ? Uncontrolled hypertension ? Prior history of hypertensive crisis or hypertensive encephalopathy ? Significant cardiovascular/cerebrovascular disease within 3 months prior to randomization ? Left ventricular ejection fraction (LVEF) = hemorrhage or bleeding event within 28 days prior to initiation of study treatment ? Clinically significant hematuria, hematemesis, hemoptysis of >0.5 teaspoon (2.5 mL) of red blood, coagulopathy, or other history of significant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To evaluate the efficacy of Arm A (tobemstomig + axitinib) vs. Control Arm (pembrolizumab+ axitinib) and Arm B (Tiragolumab + tobemstomig + axitinib) vs. Control Arm in the Full Analysis Set (FAS) ? To evaluate the safety and tolerability of Arm A vs. Control Arm and Arm B vs. Control Arm in the safety evaluable (SE) population;Secondary Objective: ? To evaluate the efficacy of Arm A vs. Control Arm and Arm B vs. Control Arm ? To evaluate the immune response to tiragolumab, and tobemstomig ;Primary end point(s): 1. Progression-free survival, defined as the time from randomization to the first occurrence of disease progression according to RECIST version 1.1, as assessed by the investigator, or death from any cause, whichever occurs first 2. Incidence and severity of adverse events, with severity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. with the exception of cytokine release syndrome (CRS) event severity which will be determined according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading scale;Timepoint(s) of evaluation of this end point: 1-2. Up to 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival (OS) defined as the time from randomization to death from any cause 2. Confirmed objective response rate (ORR) defined as the proportion of participants with a CR or PR on two consecutive occasions at least 4 weeks apart as determined by the investigator according to RECIST v1.1 3. Duration of response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 4. Prevalence of anti-drug antibodies (ADAs) to tiragolumab at baseline and incidence of ADAs to tiragolumab during the study 5. Prevalence of ADAs to tobemstomig at baseline and incidence of ADAs to tobemstomig during the study.;Timepoint(s) of evaluation of this end point: 1-3. Up to 24 months 4. Day 1 of Cycle 1; Day 1 of Cycle 2, 3, 4, 8, 12, 16; at end of treatment visit 5. Day 1 of every cycle; Day 8 and 15 of Cycle 5; at end of treatment visit | — |
Countries
Australia, China, France, Germany, Korea, Republic of, Poland, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed