Clinical trial NCT02729896: A Study Evaluating Safety and Efficacy of Obinutuzumab, Polatuzumab Vedotin (Pola), and Atezolizumab (Atezo) in Participants With Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab, Atezo, and Pola in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Official title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-04-06
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab + Atezo + Pola in participants with relapsed or refractory (RR) FL and rituximab + Atezo + Pola in participants with RR DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for Pola in this treatment combination, followed by an expansion phase in which Pola will be given at the RP2D. All participants will receive induction treatment with obinutuzumab + Atezo + Pola for 6 cycles. RR FL participants achieving a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOI) will receive maintenance treatment with obinutuzumab.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* For obinutuzumab + Atezo + Pola treatment group: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-Cluster of Differentiation (CD)20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
* For rituximab + Atezo + Pola treatment group: relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in participants who are not eligible for second line combination (immuno-) chemotherapy and autologous stem-cell transplantation or who have failed second line combination (immuno-) chemotherapy or experienced disease progression following autologous stem-cell transplantation
* Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is PET-positive lymphoma) with at least one bi-dimensionally measurable lesion
* Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
* For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use contraceptive methods that result in a failure rate of less than (\<) 1% per year during the treatment period for greater than or equal to (\>=) 5 months after last dose of Atezo, \>= 12 months after last dose of rituximab, \>= 12 months after last dose of Pola, and \>= 18 months after last dose of obinutuzumab
* For men: agreement to remain abstinent or to use contraceptive measures that result in a failure rate of \<1% per year during the treatment period and for at least 3 months after last dose of obinutuzumab, rituximab, and Atezo and for 5 months after last dose of Pola, and agreement to refrain from donating sperm during this same period

Exclusion Criteria:

* Grade 3b follicular lymphoma
* History of transformation of indolent disease to DLBCL
* Known CD20-negative status at relapse or progression; CNS lymphoma or leptomeningeal infiltration
* Prior allogeneic stem cell transplantation (SCT), completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 (D1C1)
* Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies
* Treatment with systemic immunosuppressive medications, including but not limited to prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to D1C1
* History of solid organ transplantation and of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies
* Active infection; positive for hepatitis B surface agent (HbsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening; known history of HIV positive status, progressive multifocal leukoencephalopathy (PML), autoimmune disease
* Vaccination with a live virus vaccine or live attenuated vaccine within 28 days prior to D1C1
* Pre-existing Grade greater than (\>) 1 neuropathy
* Major surgical procedure other than for diagnosis within 28 days prior to D1C1
* Inadequate hematologic function, renal function, and liver function
* Pregnant or lactating women
* Life expectancy \< 3 months

Primary outcomes:
measure: Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Secondary outcomes:
measure: Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
measure: Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
measure: Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
measure: Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: Baseline up to 35 months
measure: Percentage of Participants With Adverse Events and Serious Adverse Events
timeFrame: Baseline up to 35 months
measure: Serum Obinutuzumab Concentration
timeFrame: Pre-dose (0 hr) up to 35 months
measure: Serum Rituximab Concentration
timeFrame: Pre-dose (0 hr) up to 35 months
measure: Serum Atezo Concentration
timeFrame: Pre-dose (0 hr) up to 35 months
measure: Serum Pola Concentration
timeFrame: Pre-dose (0 hr) up to 35 months
measure: Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
timeFrame: Baseline up to 35 months
measure: Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
timeFrame: Baseline to 35 months
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo
timeFrame: Baseline to 35 months
measure: Percentage of Participants With ATAs to Pola
timeFrame: Baseline to 35 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Miami
country: United States
facility: University Miami
state: Florida
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Kennewick
country: United States
facility: Columbia Basin Hem-Onc; Department Hematology Oncology
state: Washington
city: Morgantown
country: United States
facility: Robert Byrd Health Science; Dept of Medicine, Section of Hematology/Oncology
state: West Virginia
city: Dessau-Roßlau
country: Germany
facility: Städtisches Klinikum Dessau Klinik für Innere Medizin Abt. Intensivmedizin
city: Essen
country: Germany
facility: Uniklinik Essen
city: Frankfurt
country: Germany
facility: Universitatsklinikum Frankfurt
city: Greifswald
country: Germany
facility: Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
city: Hannover
country: Germany
facility: Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
city: Jena
country: Germany
facility: Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Wuerzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Gdynia
country: Poland
facility: Szpitale Wojewodzkie w Gdyni Sp. z o.o.
city: Lodz
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego
city: Warsaw
country: Poland
facility: Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
city: Wroclaw
country: Poland
facility: Medical Uni of Wroclaw; Hematology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Topp MS, Eradat H, Florschutz A, Hochhaus A, Wrobel T, Walewski J, Knopinska-Posluszny W, Kanate AS, Lech-Maranda E, Brunnberg U, Chitra S, Nielsen TG, Sellam G, Shivhare M, Lossos IS. Anti-CD20-atezolizumab-polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma. J Cancer Res Clin Oncol. 2023 Feb;149(2):811-817. doi: 10.1007/s00432-021-03847-5. Epub 2022 Feb 18.