A phase II, randomized, open-label, national, multicenter study evaluating the efficacy and safety of the combination of atezolizumab and bevacizumab as neoadjuvant plus adjuvant treatment in hepatocellular carcinoma (ASPIRE)
- Trial ID
- 2025-521459-22-00
- Protocol
- ASPIRE
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate recurrence-free survival (RFS) in patients with resectable hepatocellular carcinoma at high risk of recurrence following treatment with atezolizumab and bevacizumab in the neoadjuvant and adjuvant setting. This endpoint is clinically relevant as it assesses the ability of immunotherapy-based combinations to prevent disease recurrence after curative-intent resection in high-risk patients.
The secondary objectives include:
• Assessment of pathological response, including both major pathological response (MPR) and complete pathological response (pCR), to neoadjuvant therapy at the time of surgical resection.
• Evaluation of overall survival (OS).
• Evaluation of treatment efficacy by assessing event-free survival (EFS) and objective response rate (ORR) with neoadjuvant atezolizumab plus bevacizumab treatment combinations.
• Evaluation of the safety and tolerability of neoadjuvant and adjuvant atezolizumab and bevacizumab treatment combinations.
• Assessment of surgical feasibility, outcomes, morbidity, and mortality in participants receiving neoadjuvant immunotherapy-based treatment combinations.
Participants
The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted of adult participants aged 18 years and older, including both male and female subjects. Participants were patients diagnosed with resectable **hepatocellular carcinoma** at high risk of recurrence, confirmed by histology and amenable to R0 surgical resection with curative intent. The trial included individuals with **Child-Pugh Class A** liver function and an **Eastern Cooperative Oncology Group Performance Status** of 0, indicating fully active patients without performance restrictions. Participants were required to have measurable disease according to **RECIST v1.1** criteria and adequate hematologic and end-organ function, including specific thresholds for absolute neutrophil count, lymphocyte count, platelet count, hemoglobin, liver enzymes, bilirubin, renal function, and albumin levels. The population included patients with documented **hepatitis B virus** or **hepatitis C virus** status, with specific requirements for viral load management and antiviral treatment. Patients with controlled **HIV** infection were eligible if stable on antiretroviral therapy with adequate CD4 counts and undetectable viral load. High-risk features defining the study population included tumor multifocality, large tumor diameter exceeding 5 cm, elevated **alpha-fetoprotein** levels of 400 ng/mL or higher, poor tumor differentiation, or presence of **microvascular invasion**. Participants were treatment-naïve, having received no prior locoregional or systemic therapy for hepatocellular carcinoma. Women of childbearing potential and male participants were required to use contraception or remain abstinent during the study period.
Plans and Procedures
This is a phase II, randomized, open-label, national, multicenter clinical trial evaluating the efficacy and safety of combination therapy with **atezolizumab** and **bevacizumab** as neoadjuvant plus adjuvant treatment in patients with resectable **hepatocellular carcinoma** at high risk of recurrence. The study employs a randomized design without blinding, allowing both investigators and participants to be aware of treatment assignment. The trial is designed to assess the therapeutic potential of combining two **monoclonal antibodies** administered as **solution for infusion** via **infusion** route in the perioperative setting.
The primary objective is to evaluate **recurrence-free survival**, defined as the time from randomization to first documented disease recurrence according to **RECIST v1.1** and **mRECIST** criteria by the investigator's radiology team, or death from any cause, whichever occurs first. Secondary endpoints include **major pathological response** rate, defined as the proportion of participants with greater than 70% tumor necrosis in the tumor bed at surgery as assessed by central pathological review, **complete pathological response** rate defined as absence of residual tumor at surgery, **overall survival** defined as time from randomization to death from any cause, **event-free survival** defined as time from randomization to predefined events including disease progression or toxicity precluding surgery, relapse, or death, **objective response rate** defined as the proportion of participants with radiological complete response or partial response prior to surgery, **R0 resection** rate defined as microscopically margin-negative resection with no gross or microscopic tumor remaining in the primary tumor bed, incidence and severity of adverse events including immune-related adverse events graded according to **NCI CTCAE v5.0**, proportion of participants with delayed or canceled surgery defined as greater than 28 days from surgical restaging visit, postoperative surgical complication rates according to the **Clavien-Dindo** surgical classification with clinically relevant complications defined as grade IIIa or higher, and postoperative mortality defined as death within 90 days after surgery.
Eligible participants must be at least 18 years of age with histologically confirmed hepatocellular carcinoma amenable to R0 surgical resection with curative intent. High risk of recurrence is defined by multifocality, large tumor diameter greater than 5 cm, **alpha-fetoprotein** level of 400 ng/mL or higher, poor tumor differentiation, or presence of **microvascular invasion**. For tumors between 3 to 5 cm, a predefined nomogram indicating high prevalence of microvascular invasion with a score greater than 200 points will be applied. Participants must have measurable disease with at least one target lesion according to RECIST v1.1, **Eastern Cooperative Oncology Group Performance Status** of 0, and **Child-Pugh Class A** liver function. No evidence of **clinically significant portal hypertension** or minor clinically significant portal hypertension with **hepatic venous pressure gradient** less than 12 mmHg is required for candidates undergoing minor resection of fewer than 3 segments. Clinically significant portal hypertension can be defined by hepatic venous pressure gradient of 10 mmHg or greater, or by surrogate markers such as **platelet count** less than 100,000 × 10³/µL combined with **splenomegaly**.
Participants must have adequate hematologic and end-organ function including **absolute neutrophil count** of 1.5 × 10⁹/L or greater without **granulocyte colony-stimulating factor** support, **lymphocyte count** of 0.5 × 10⁹/L or greater, platelet count of 75 × 10⁹/L or greater without transfusion, **hemoglobin** of 90 g/L or greater without transfusion within 2 weeks prior to screening, **aspartate aminotransferase**, **alanine aminotransferase**, and **alkaline phosphatase** of 5 times **upper limit of normal** or less, **bilirubin** of 3 times upper limit of normal or less, adequate renal function with **creatinine clearance** by **estimated glomerular filtration rate** using **Modification of Diet in Renal Disease Study** formula of 50 mL/min or greater, **albumin** of 28 g/L or greater without transfusion, and for participants not receiving anticoagulation, **international normalized ratio** or **activated partial thromboplastin time** of 1.5 times upper limit of normal or less. Documented virology status must be confirmed with screening tests for **hepatitis B virus** and **hepatitis C virus**. Patients with active hepatitis B virus must have **HBV DNA** less than 500 IU/mL during screening, must have initiated anti-hepatitis B virus treatment at least 14 days prior to treatment initiation, and must continue treatment during the study. Patients with hepatitis C virus with either resolved infection evidenced by detectable antibody or chronic infection evidenced by detectable **HCV RNA** are eligible. For patients with detectable HCV RNA for whom hepatitis C virus treatment is considered appropriate, treatment should begin no sooner than 6 months following liver resection. Negative **HIV** test at screening is required, with the exception that individuals with positive HIV test are eligible if stable on **anti-retroviral therapy** with **CD4 count** of 200/mL or greater and undetectable viral load.
Participants must be willing to undergo tumor biopsy at screening visit. Baseline tumor tissue samples will be collected from all participants by core-needle biopsy performed at study entry with a minimum of two core-needle biopsies required. If fresh biopsy is not deemed feasible by the investigator, archival tumor tissue may be submitted provided the tissue was obtained from biopsy performed within 3 months prior to enrollment and the patient has not received any anti-cancer therapy including locoregional liver-directed therapy since the time of biopsy. Tumor and normal adjacent tissue specimens will be collected at surgery as fresh snap-frozen and **formalin-fixed, paraffin-embedded** format. Formalin-fixed, paraffin-embedded tissue blocks are preferred, or a minimum of 20 slides must be submitted. No prior locoregional or systemic treatment for hepatocellular carcinoma is permitted. Signed informed consent form is required, and participants must have the ability to fully comply with the protocol in the investigator's judgment.
**Atezolizumab** will be administered at a maximum daily dose of 1200 mg with a maximum total dose of 24,000 mg over a maximum treatment period of 14 months. **Bevacizumab** will be administered at a maximum daily dose of 15 mg/kg with a maximum total dose of 285 mg/kg over a maximum treatment period of 14 months. Both investigational medicinal products are manufactured by Roche Registration GmbH and are administered as solution for infusion via infusion route. For women of childbearing potential, agreement to remain abstinent or use contraception is required. For men, agreement to remain abstinent or use contraception and agreement to refrain from donating sperm is required.
The estimated recruitment start date is November 10, 2025, with an estimated study end date of November 10, 2030, indicating an overall trial duration of approximately 5 years. The screening visit includes assessment of eligibility criteria, collection of baseline tumor tissue samples, and confirmation of virology status. Participants will undergo neoadjuvant treatment followed by surgical resection with collection of tumor and normal adjacent tissue specimens. Following surgery, participants will receive adjuvant treatment. Follow-up visits will be conducted to assess disease recurrence, survival outcomes, and safety parameters. The end-of-study visit will occur at the completion of follow-up period or upon study discontinuation. Participant involvement is expected to extend throughout the neoadjuvant treatment phase, surgical intervention, adjuvant treatment phase, and subsequent follow-up period for assessment of recurrence-free survival and overall survival.
Early termination from the study may occur due to disease progression or toxicity precluding surgery, withdrawal of consent, unacceptable adverse events, protocol violations, loss to follow-up, death, or investigator decision that continued participation is not in the best interest of the participant. Surgical delay or cancellation is defined as greater than 28 days from surgical restaging visit, and such delays will be documented along with reasons for delay, duration of surgery, length of hospital stay, surgical approach, extent of surgery, intraoperative blood loss, and need for intraoperative blood transfusion.
Treatment
The experimental treatment regimen consists of two investigational medicinal products administered in combination for the treatment of **hepatocellular carcinoma**. Both agents are **monoclonal antibodies** administered as neoadjuvant plus adjuvant therapy in this phase II, randomized, open-label, national, multicenter study.
**Atezolizumab** is administered as the first experimental agent under the trade name **Tecentriq** 1 200 mg concentrate for **solution for infusion**. The active substance is atezolizumab, a protein-based monoclonal antibody. The pharmaceutical form is a concentrate for solution for infusion, prepared as a solution for infusion prior to administration. The route of administration is **intravenous infusion**. The maximum daily dose is **1200 mg**. The maximum total dose amount is **24000 mg** over a treatment period of **14 months**. The product is manufactured by Roche Registration GmbH and holds marketing authorization number EU/1/17/1220/001.
**Bevacizumab** is administered as the second experimental agent under the trade name **Avastin** 25 mg/ml concentrate for solution for infusion. The active substance is bevacizumab, a protein-based monoclonal antibody. The pharmaceutical form is a concentrate for solution for infusion, prepared as a solution for infusion prior to administration. The route of administration is intravenous infusion. The dosing is weight-based, with a maximum daily dose of **15 mg/kg**. The maximum total dose amount is **285 mg/kg** over a treatment period of **14 months**. The product is manufactured by Roche Registration GmbH and holds marketing authorization number EU/1/04/300/002.
Both investigational products are administered according to a defined dosing schedule throughout the neoadjuvant and adjuvant treatment phases. The study evaluates the efficacy and safety of this combination regimen, with the main objective being the assessment of **recurrence-free survival**. Participant compliance monitoring is conducted throughout the treatment period to ensure adherence to the prescribed dosing regimen and administration schedule.
Efficacy
Efficacy will be assessed using recurrence-free survival as the primary endpoint, defined as the time from randomization to the first documented recurrence of disease according to RECIST v1.1 and mRECIST by the investigator's radiology team, or death from any cause, whichever occurs first. Secondary efficacy endpoints include major pathological response rate, defined as the proportion of participants with greater than 70% necrosis of tumor in the tumor bed at the time of surgery, as assessed by central pathological review. Complete pathological response rate will be evaluated, defined as the proportion of participants with an absence of residual tumor at the time of surgery, as assessed by central pathological review. Overall survival will be measured as the time from randomization to death from any cause. Event-free survival will be assessed as the time from randomization to predefined events, which may include disease progression or toxicity precluding surgery, relapse assessed according to RECIST v1.1 and mRECIST by the investigator's radiology team, or death. Objective response rate will be determined as the proportion of participants with a radiological complete response or partial response prior to surgery, as determined by the investigator according to RECIST v1.1 and HCC mRECIST. The R0 resection rate will be evaluated as the proportion of resected participants obtaining an R0 resection, defined as a microscopically margin-negative resection in which no tumor remains in the primary tumor bed. Additional assessments will include the proportion of participants with delayed or canceled surgery, defined as greater than 28 days from surgical restaging visit, as well as length of surgical delay, duration of surgery, length of hospital stays, surgical approach, extent of surgery, intraoperative blood loss, and need for intraoperative blood transfusion. Post-operative surgical complication rates will be assessed according to the Clavien-Dindo surgical classification, with clinically relevant complications defined as Clavien-Dindo Grade IIIa or higher. Post-operative mortality will be evaluated as death within 90 days after surgery.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed Informed Consent Form.
- Age ≥ 18 years at the time of signing Informed Consent Form.
- Ability to fully comply with the protocol, in the investigator's judgment.
- Diagnosis of HCC confirmed by histology.
- HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant.
- HCC at high-risk of recurrence defined by either multifocality, large tumor diameter (>5cm), AFP (alpha-fetoprotein) ≥400ng/mL, poor tumor differentiation, or the presence of microvascular invasion. For patients with tumors between 3-5 cm, a predefined nomogram will be applied, indicating a high prevalence of microvascular invasion with a score >200 points. (Lie et al., 2016)
- Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0.
- Child-Pugh Class A.
- No evidence of clinically significant portal hypertension (CSPH) or minor CSPH (HVPG <12 mmHg) in candidates for minor resection (fewer than 3 segments). (Galle et al., 2018) Clinically significant portal hypertension (CSPH) can be defined either by its gold standard measurement, a hepatic venous pressure gradient (HVPG) ≥10 mmHg, or by the presence of surrogate markers such as a platelet count <100,000 × 10³/µL combined with splenomegaly.
- Willing to undergo a tumor biopsy at screening visit. - Baseline tumor tissue samples will be collected from all participants by means of a core-needle biopsy performed at study entry. A minimum of two core-needle biopsies are required. If a fresh biopsy is not deemed feasible by the investigator, archival tumor tissue may be submitted, provided the tissue was obtained from a biopsy performed within 3 months prior to enrollment and the patient has not received any anti-cancer therapy, including locoregional liver-directed therapy, since the time of the biopsy. Tumor and normal adjacent tissue specimen will be collected at surgery as fresh snap-frozen and formalin-fixed, paraffin‑embedded (FFPE) format. FFPE tissue blocks are preferred, or a minimum of 20 slides must be submitted.
- No prior locoregional or systemic treatment for HCC.
- Adequate hematologic and end-organ function, defined by the following laboratory test results: - ANC ≥ 1.5 × 109/L (1500/µL) without granulocyte colony-stimulating factor (G‑CSF) support. - Lymphocyte count ≥ 0.5 × 109/L (500/µL). - Platelet count ≥ 75 × 109/L (75,000/µL) without transfusion. - Hemoglobin ≥ 90 g/L (9.0 g/dL) without transfusion. Participants must not have required transfusion during screening or within 2 weeks prior to screening to meet this criterion. - AST, ALT, and ALP ≤ 5 × upper limit of normal (ULN). - Bilirubin ≤ 3 × ULN. - Adequate renal function: creatinine clearance by estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease Study (MDRD) formula ≥ 50 mL/min Participants with creatinine clearance by estimating eGFR by MDRD formula of ≥ 30 mL/min and ≤ 50 mL/min may be enrolled if renal function was stable for ≥ 28 days prior to randomization. - Albumin ≥ 28 g/L (2.8 g/dL) without transfusion. - For participants not receiving anticoagulation: INR or aPTT ≤ 1.5 × ULN.
- Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus (HBV) and/or hepatitis C virus (HCV): - Patients with active HBV must have HBV DNA < 500 IU/mL during screening, must have initiated anti-HBV treatment at least 14 days prior treatment initiation, and must be willing to continue anti‑HBV treatment during the study (per local standard of care, e.g., entecavir). - Patients with HCV, either with resolved infection (as evidenced by detectable antibody) or chronic infection (as evidenced by detectable HCV RNA), are eligible. - For patients with detectable HCV RNA and for whom HCV treatment is considered appropriate by the investigator, treatment should begin no sooner than 6 months following liver resection consistent with AASLD guidelines.
- Negative HIV test at screening with the following exception: - Individuals with a positive HIV test at screening are eligible if they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/mL, and have an undetectable viral load.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm.
Exclusion Criteria
- Presence of extrahepatic disease or macrovascular invasion.
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding. Participants must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Participants who have undergone an EGD within 6 months prior screening do not need to repeat the procedure.
- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to screening.
- Inadequately controlled hypertension, defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg (average of at least three readings at two or more sessions). Anti-hypertensive therapy to achieve these parameters is allowed.
- History of hypertensive crisis or hypertensive encephalopathy.
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to screening.
- History of hemoptysis (≥ 2.5 mL of bright red blood per episode) within 1 month prior to screening.
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- Current or recent (≤ 10 days prior to screening) use of aspirin (> 325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol. Chronic use of low dose aspirin (< 325 mg/day) for cardioprotection is allowed.
- Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC.
- History of hepatic encephalopathy if clinically significant within one year prior to screening.
- CSPH in candidates for major resection (more than 3 segments).
- Moderate or severe ascites.
- Active co-infection with HBV and HCV (defined as detectable HCV RNA plus positive HBV surface antigen or HBV DNA). Patients with a history of HCV infection but who are negative for HCV RNA by Polymerase Chain Reaction (PCR) will be considered non-infected with HCV.
- Known active co-infection with HBV and hepatitis D viral infection (HDV).
- Prior treatment with immune checkpoint blockade therapies, including anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies.
- Treatment with investigational therapy within 28 days prior to screening.
- Current or recent (≤ 10 days prior to screening) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. - Prophylactic anticoagulation for the patency of venous access devices is allowed provided the activity of the agent results in an INR < 1.5 × ULN and aPTT is within normal limits within 14 days prior to screening. - Prophylactic use of low-molecular-weight heparin (LMWH; i.e., enoxaparin 40 mg/day) is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) are not recommended due to potential bleeding risk. Benefits and risks should be assessed, and caution exercised for use of direct oral anticoagulants. The investigator should consider switching to other approved anticoagulants due to the risk of upper GI (gastrointestinal) bleeding in patients with HCC. - For prophylactic use of anticoagulants or thrombolytic therapies, the approved dose as described on the local label may be used.
- History of abdominal or tracheoesophageal fistula, GI perforation, or intra‑abdominal abscess within 6 months prior to screening.
- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction, including subocclusive or occlusive syndrome related to the underlying disease, or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding prior to screening.
- Evidence of abdominal free air that is not explained by paracentesis or recent (< 3 months) abdominal surgical procedure.
- Serious, non-healing, or dehiscing wound, active ulcer, or untreated bone fracture.
- Grade ≥ 2 proteinuria, as demonstrated by ≥ 2+ protein on dipstick urinalysis and ≥ 1.0 g of protein in a 24-hour urine collection. - All patients with ≥ 2+ protein on dipstick urinalysis at screening must undergo a 24-hour urine collection (or an alternative method such as protein/creatinine ratio, per local guidance) for protein and must demonstrate < 1 g of protein in 24 hours. - Patients with < 2+ protein on dipstick urinalysis are eligible for the study.
- History of intra-abdominal inflammatory process within 6 months prior to screening, including but not limited to peptic ulcer disease, diverticulitis, or colitis.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to screening; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to screening; or anticipation of need for major surgical procedure, other than potentially curative liver resection, during the study; or non‑recovery from side effects of any such procedure.
- Complete healing from minor surgery (e.g., simple excision, tooth extraction) must have occurred at least 7 days before screening.
- Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID). - The occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed.
- Serious infection requiring oral or IV antibiotics and/or hospitalization within 4 weeks prior to screening, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact participant safety.
- Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
- History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. - Patients with localized prostate cancer (defined as Stage ≤ pT2c, Gleason score ≤ 7, and prostate-specific antigen (PSA) at prostate cancer diagnosis ≤ 20 ng/mL) treated with curative intent and without PSA recurrence are eligible. - Patients with pre-existing low-risk prostate cancer (defined as Stage cT1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible. - Patients with malignancies associated with a negligible risk of metastasis or death (e.g., risk of metastasis or death < 5% at 5 years) are eligible provided they meet all of the following criteria: o Malignancy treated with expected curative intent (e.g., adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) o No evidence of recurrence or metastasis by follow-up imaging and any disease‑specific tumor markers.
- Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: - Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. - Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. - Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: o Rash must cover < 10% of body surface area. o Disease is well controlled at baseline and requires only low-potency topical corticosteroids. o No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study. - Female participants of childbearing potential must have a negative serum pregnancy test result at screening.
- Left ventricular ejection fraction (LVEF) < 50% assessed by either transthoracic echocardiogram (TTE) or multiple-gated acquisition (MUGA) scan (TTE preferred test) within 6 months prior to screening.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis or evidence of active pneumonitis on screening chest computed tomography (CT) scan. - History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Prior allogeneic stem cell or solid organ transplantation.
- Active tuberculosis.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 10 Nov 2025 | 90 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Tecentriq 1 200 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INFUSION | 1200 | 14 | PRD5434939 |
Avastin 25 mg/ml concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INFUSION | 15 | 14 | PRD2153902 |