Sub-study 1 Cervical Cancer (Volrustomig Monotherapy), Sub-study 2 Head and Neck Squamous Cell Carcinoma (Volrustomig Monotherapy), Sub-study 3 Head and Neck Squamous Cell Carcinoma (Volrustomig in Combination With Chemotherapy), Sub-study 4 Esophageal Squamous Cell Carcinoma (Volrustomig in Combination With Chemotherapy), Sub-study 5 Unresectable Pleural Mesothelioma (Volrustomig Monotherapy)
Conditions
Keywords
Cervical Cancer, Head and Neck Squamous Cell Carcinoma, eVOLVE-02, Volrustomig, Esophageal Squamous Cell Carcinoma, Unresectable Pleural Mesothelioma
Brief summary
eVOLVE-02 study will evaluate the efficacy and safety of volrustomig as monotherapy or in combination with anti-cancer agents in participants with advanced/metastatic solid tumors.
Detailed description
eVOLVE-02 study will evaluate volrustomig monotherapy or volrustomig-based combination therapy in various advanced or metastatic solid tumors. In sub-study 1, volrustomig will be evaluated as monotherapy in approximately 30 evaluable participants with cervical cancer. In sub-study 2, volrustomig will be evaluated as monotherapy in approximately 20 evaluable participants with head and neck squamous cell carcinoma. In sub-study 3, Volrustomig in Combination with Chemotherapy will be evaluated in approximately 60 evaluable participants with head and neck squamous cell carcinoma. In sub-study 4, volrustomig in Combination with Chemotherapy will be evaluated in approximately 60 evaluable participants with esophagus squamous cell carcinoma. In sub-study 5, volrustomig will be evaluated as monotherapy in approximately 75 evaluable participants with unresectable pleural mesothelioma.
Interventions
BIOLOGICALVolrustomig
IV Infusion
DRUGCisplatin
IV Infusion
DRUGCarboplatin
IV Infusion
DRUGPaclitaxel
IV Infusion
DRUG5-FU
IV Infusion
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 at the time of signing the ICF. * Provision of tumor sample to assess the PD-L1 expression (if applicable). * ECOG performance status of 0 or 1. * Measurable disease according to RECIST 1.1 (variations of RECIST 1.1 if applicable). * Life expectancy ≥ 12 weeks. * Adequate organ and bone marrow function. * Body weight \> 35 kg * Capable of giving signed informed consent.
Exclusion criteria
* Spinal cord compression. * For sub-study 1,2,3,4, brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. For sub-study 5, participants with untreated or progressive brain metastases. * For sub-study 1,2,3, participants with primary neuroendocrine, mesenchymal, sarcomatoid histologies, or other histologies not mentioned as part of the inclusion criteria. * Have not recovered (ie, ≤ Grade 1 or at baseline) from an AE due to a previously administered anti-cancer therapy. * For sub-study 2, have had radiotherapy within 2 weeks prior to enrollment. * For sub-study 3,4, participants have contraindications to any of the following drugs: 5-FU, paclitaxel and carboplatin * History of another primary malignancy except for a) Malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention and of low potential risk for recurrence; b) Adequately treated nonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence of disease. * Any evidence of diseases, and/or history of organ transplant or allogenic stem cell transplant, which makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol. * Evidence of the following infections: active infection including tuberculosis; known HIV infection. that is not well controlled; active or uncontrolled HBV or HCV; or active hepatitis A. * History of active primary immunodeficiency or active or prior documented autoimmune or inflammatory disorders. * Participants who are candidates for curative therapy. * Prior exposure to any immune-mediated therapy. * Current or prior use of immunosuppressive medication within 14 days before the first dose of the study intervention is excluded. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection); b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication or chemotherapy premedication) or a single dose for palliative purpose (eg, pain control). * For sub-study 1,2,3,4, participants are ineligible if they have received any anti-cancer therapy within 28 days prior to the first dose of study intervention or within 5 half-lives of the respective agent, whichever is longer. * Any concurrent chemotherapy except study intervention, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. * Radiotherapy treatment with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention. * Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery. * Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention. * Participants with a known allergy or hypersensitivity to any study intervention, on any excipients of any study intervention. * For substudy 5: Participants with any prior systemic therapy, non-palliative radiotherapy, radical pleuropneumonectomy for pleural mesothelioma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Through study completion, an average of 4 years | Confirmed ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by Investigator per RECIST 1.1. |
| The number of participants with adverse events/serious adverse events | Through study completion, an average of 4 years | Number of participants with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration Of Response (DOR) | Through study completion, an average of 4 years | DoR is defined as the time from the date of first documented confirmed response (which is subsequently confirmed) until date of documented progression per RECIST 1.1 as assessed by Investigator or ICR, or death due to any cause. |
| Progression free survival (PFS) | Through study completion, an average of 4 years | PFS is defined as the time from date of first dose of study intervention until progression per RECIST 1.1 as assessed by Investigator or ICR, or death due to any cause. |
| Time to response (TTR) | Through study completion, an average of 4 years | TTR is defined as the time from the date of the first dose of study intervention until the date of first documented objective response, which is subsequently confirmed per RECIST 1.1, as assessed by Investigator or ICR. |
| Overall Survival (OS) | Through study completion, an average of 4 years | OS is defined as the time from the date of first dose of study intervention until the date of death due to any cause. |
| PK of volrustomig | Through study completion, an average of 4 years | Concentration of Volrustomig in serum. |
| The immunogenicity of volrustomig | Through study completion, an average of 4 years | Incidence of ADAs against volrustomig in serum. |
| Disease control rate (DCR) | Through study completion, an average of 4 years | Disease control rate is defined as the proportion of participants with a BOR of confirmed CR, confirmed PR, or SD, as determined by Investigator per RECIST 1.1. |
| PFS landmark | Through study completion, an average of 4 years | The landmark of PFS rates at 6, 9, and 12 months. |
| OS landmark | Through study completion, an average of 4 years | The median OS and the landmark of OS rate at 12 months. |
Countries
Australia, Brazil, Canada, China, Germany, Italy, Japan, South Korea, Taiwan, United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed