This multicenter, double-blind, placebo-controlled, randomized study will evaluate the efficacy and safety of the addition of bevacizumab treatment to lomustine (in 2nd-line [2L] treatment) and SOC (in 3rd-line [3L] and subsequent lines of treatment) following first-line disease progression (PD1) in participants with newly diagnosed glioblastoma. All enrolled participants will receive 1L treatment with radiotherapy, temozolomide, and bevacizumab. At PD1, eligible participants will be randomized (1:1) to receive 2L treatment with either bevacizumab plus lomustine or placebo plus lomustine. After second-line disease progression (PD2), participants will receive 3L treatment and will continue blinded bevacizumab or placebo with the addition of an SOC agent. Following third-line disease progression (PD3), participants will receive subsequent lines of treatment and will either continue blinded bevacizumab or placebo (at the discretion of the investigator), or switch to open-label bevacizumab (at the choice of the participant).

Inclusion Criteria at Enrollment (before PD1):

• Newly diagnosed, histologically confirmed glioblastoma not previously treated with chemotherapy or radiotherapy
• If female and not postmenopausal (less than [<] 12 months of amenorrhea) or surgically sterile, must agree to use a highly effective contraceptive method during the treatment period and for at least 6 months after the last dose of study drug
• Karnofsky performance status (KPS) greater than or equal to (>/=) 60
• Mandatory tissue collection during pre-study surgery or biopsy for confirmation of the diagnosis and pathology
• Craniotomy or intracranial biopsy site must be adequately healed. Study treatment should be initiated > 28 days following the last surgical procedure

Inclusion Criteria at Randomization (following PD1):

• Documented PD1 according to RANO criteria
• Eligibility for second-line treatment with lomustine and bevacizumab as investigational medicinal products
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Bevacizumab well tolerated and not interrupted for longer than 60 days during first-line treatment
• Tissue submission among participants for whom operation/re-operation is indicated before second-line treatment starts; operation/re-operation performed >/=28 days after last bevacizumab administration and second-line treatment initiated >/=28 days after surgical wound healed
• Randomization within 28 days after PD1 among participants for whom operation/re-operation is not necessary
• First administration of second-line treatment no later than 2 days from randomization

Exclusion Criteria at Enrollment (before PD1):

• Any prior chemotherapy for glioblastoma and low-grade astrocytomas
• Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field
• Prior or current anti-angiogenic treatment
• Treatment with any other investigational drug within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first study treatment
• Inadequate hematological, renal, or liver function
• Inadequately controlled hypertension
• Prior history of gastrointestinal perforation or abscess
• Clinically significant cardiovascular disease
• History or evidence of central nervous system disease unrelated to cancer unless adequately treated with standard medical therapy
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
• Serious non-healing wound, active ulcer, or untreated bone fracture
• Known hypersensitivity to any component of bevacizumab/placebo or any of the study drugs
• Active infection requiring IV antibiotics at start of study treatment
• Other malignancy within 5 years prior to study enrollment, except for carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ treated with curative intent
• Pregnant or lactating women
• Participation in any other study