An open label, multicenter extension study in patients previously enrolled in a Genentch and/or F. Hoffmann-La Roche Ltd sponsored atezolizumab study (IMBRELLA B)

The primary objective of this study is to provide continued treatment with atezolizumab-based therapy and/or combination/comparator agents for eligible patients still on study treatment at the time of roll-over from the parent study who do not have access to the study treatment locally. This extension trial addresses the clinical need to ensure uninterrupted access to potentially beneficial investigational therapies for patients with advanced malignancies who have demonstrated clinical benefit in prior atezolizumab-sponsored studies. The primary objective is clinically relevant as it allows patients to continue receiving treatment that may be providing therapeutic benefit while commercial availability or alternative access mechanisms are not yet established in their local healthcare setting.

The secondary objective is to identify any new safety signal related to atezolizumab or atezolizumab administered with combination agent(s) in patients who are currently eligible to receive treatment with atezolizumab and have demonstrated clinical benefit. This secondary endpoint is important for ongoing pharmacovigilance and characterization of the long-term safety profile of atezolizumab-based regimens in patients with extended treatment exposure.

This extension clinical trial enrolled a total of **1000 participants** diagnosed with **advanced malignancies**. The study population included both **male and female subjects** across **adult and elderly age groups**. Participants were selected based on their enrollment and active treatment status in a parent study, specifically those who were eligible to continue **atezolizumab-based therapy** or comparator agents and who continued to derive clinical benefit from the treatment at the time of rollover. Key inclusion criteria required participants to have received their last dose in the parent study within the permitted interruption period, with the first dose in the extension study administered within 7 days of the allowable treatment interruption window. The trial population included **vulnerable populations**. Participants were required to demonstrate the ability to comply with study requirements and, for women of childbearing potential, to have a negative serum pregnancy test and adhere to contraception requirements. The trial was designed to provide continued access to study treatment for patients without local availability of the therapy.

This open-label, multicenter extension study provides continued treatment with atezolizumab-based therapy and/or combination/comparator agents for patients who were previously enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd sponsored atezolizumab study and remain on study treatment at the time of rollover. The study is designed as a Phase III clinical trial conducted across multiple European countries including Germany, Belgium, Czechia, France, Greece, Hungary, Latvia, Poland, Romania, Slovakia, and Spain. The trial involves patients with advanced malignancies, including conditions such as non-small cell lung cancer, metastatic melanoma, renal cell carcinoma, urothelial carcinoma, triple negative breast cancer, ovarian cancer, squamous cell carcinoma of head and neck, and other solid tumors.

The primary objective is to provide access to atezolizumab-based therapy for eligible patients who continue to derive clinical benefit from treatment and do not have local access to the study medication. The study employs various investigational medicinal products administered via oral and intravenous routes, including alectinib hydrochloride, sunitinib, cabozantinib, pemetrexed, cobimetinib, vemurafenib, paclitaxel, niraparib, venetoclax, and atezolizumab. The maximum treatment period is set at 120 months, with daily doses varying according to the specific medicinal product administered.

Principal inclusion criteria require patients to have signed the extension study informed consent form and to be eligible for continuing atezolizumab-based therapy or comparator agents at the time of rollover from the parent study. Patients must continue to benefit from study treatment as assessed by the investigator and must be able to comply with study requirements. The time between the last dose in the parent study and the first dose in the extension study must not exceed the interruption period allowed in the parent study, with the first dose to be received within 7 days of the treatment interruption window. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to start of study treatment and must comply with contraception criteria.

The primary endpoint assesses patients who are deriving clinical benefit from treatment with atezolizumab-based therapy and/or comparator agents according to investigator assessment. The study commenced recruitment on 31 December 2018 and is estimated to conclude on 31 December 2028. Participant involvement extends for the duration of continued clinical benefit from treatment, up to a maximum of 120 months. Early termination from the study may occur if patients no longer derive clinical benefit from treatment, experience unacceptable toxicity, withdraw consent, or if the investigator determines that continued participation is not in the patient's best interest.

Alecensa 150 mg hard capsules contains alectinib hydrochloride as the active substance in a capsule, hard pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 1200.00 mg, with a maximum total dose of 151200.00 mg over a treatment period of up to 120 months. The product is manufactured by ROCHE REGISTRATION GMBH and holds a marketing authorisation number EU/1/16/1169/002. The active substance is of chemical origin.

Sutent 50 mg hard capsules contains sunitinib as the active substance in a capsule, hard pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 50.00 mg, with a maximum total dose of 8400.00 mg over a treatment period of up to 120 months. The product is manufactured by PFIZER EUROPE MA EEIG and holds a marketing authorisation number EU/1/06/347/003. The active substance is of chemical origin.

RO7047650 contains cabozantinib as the active substance in a film-coated tablet pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 60 mg, with a maximum total dose of 7560.00 mg over a treatment period of up to 120 months. The product is manufactured by EXELIXIS. The active substance is of chemical origin.

ALIMTA 500 mg powder for concentrate for solution for infusion contains pemetrexed as the active substance. The medicinal product is administered via the intravenous route. The maximum daily dose is 1415.00 mg, with a maximum total dose of 8490.00 mg over a treatment period of up to 120 months. The product is manufactured by ELI LILLY NEDERLAND B.V. and holds a marketing authorisation number EU/1/04/290/001. The active substance is of chemical origin.

Cotellic contains cobimetinib as the active substance in a film-coated tablet pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 60.00 mg, with a maximum total dose of 7560.00 mg over a treatment period of up to 120 months. The product is manufactured by F. HOFFMANN-LA ROCHE LTD. The active substance is of chemical origin.

Alectinib (Alecensa) contains alectinib as the active substance in a capsule, hard pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 1200.00 mg, with a maximum total dose of 151200.00 mg over a treatment period of up to 120 months. The product is manufactured by F. HOFFMANN-LA ROCHE LTD. The active substance is of chemical origin.

Zelboraf contains vemurafenib as the active substance in a film-coated tablet pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 1440.00 mg, with a maximum total dose of 241920.00 mg over a treatment period of up to 120 months. The product is manufactured by F. HOFFMANN-LA ROCHE LTD. The active substance is of chemical origin.

Paclitaxel 6 mg/ml Concentrate for Solution for Infusion contains paclitaxel as the active substance. The medicinal product is administered via the intravenous route. The maximum daily dose is 261.00 mg, with a maximum total dose of 4698.00 mg over a treatment period of up to 120 months. The product is manufactured by ACCORD HEALTHCARE LIMITED and holds a marketing authorisation number PL 20075/0128. The active substance is of chemical origin.

Sutent 12.5 mg hard capsules contains sunitinib as the active substance in a capsule, hard pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 50.00 mg, with a maximum total dose of 8400.00 mg over a treatment period of up to 120 months. The product is manufactured by PFIZER EUROPE MA EEIG and holds a marketing authorisation number EU/1/06/347/001. The active substance is of chemical origin.

RO7250726 contains niraparib as the active substance in a capsule, hard pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 200.00 mg, with a maximum total dose of 33600.00 mg over a treatment period of up to 120 months. The product is manufactured by GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LIMITED. The active substance is of chemical origin.

Venclexta, Venclyxto contains venetoclax as the active substance in a film-coated tablet pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 1200.00 mg, with a maximum total dose of 134400.00 mg over a treatment period of up to 120 months. The product is manufactured by ABBVIE, INC. and has been designated as an orphan drug under designation number EU/3/17/1954. The active substance is of chemical origin.

Tecentriq 1 200 mg concentrate for solution for infusion contains atezolizumab as the active substance. The medicinal product is administered via the intravenous route. The maximum daily dose is 1200.00 mg, with a maximum total dose of 10080.00 mg over a treatment period of up to 120 months. The product is manufactured by ROCHE REGISTRATION GMBH and holds a marketing authorisation number EU/1/17/1220/001. The active substance is of protein origin.

Sutent 25 mg hard capsules contains sunitinib as the active substance in a capsule, hard pharmaceutical form. The medicinal product is administered via the oral route. The maximum daily dose is 50.00 mg, with a maximum total dose of 8400.00 mg over a treatment period of up to 120 months. The product is manufactured by PFIZER EUROPE MA EEIG and holds a marketing authorisation number EU/1/06/347/002. The active substance is of chemical origin.

Efficacy will be assessed based on clinical benefit derived from treatment with **atezolizumab-based therapy** and/or comparator agent(s) according to investigator assessment. Patients continuing to benefit from atezolizumab-based study treatment or from the comparator at the time of roll-over from the parent study will be evaluated throughout the extension study period. The assessment will be conducted by the investigator to determine whether patients remain eligible for continued treatment based on ongoing clinical benefit.