NP30179 Eligibility Screening Form (ESF) Version 3.0

Transcription

1 (ESF) Version 3.0 Site Number: birthdate: Screening number: page 1/6 Patients must meet the following criteria for study entry: Inclusion Criteria Note that if any box is marked NO, the patient is not eligible for enrollment. 1 Signed Informed Consent(s) Forms Patient must be willing and able to comply with protocol-mandated hospitalization upon administration of the first dose of RO Age 18 years. Depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express CD20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [SCT]). Eligible r/r NHL patients include: For Parts I and II: Grades 1-3b FL; MZL (splenic; nodal; extra-nodal); MCL; DLBCL; PMBCL; Richter s transformation; and/or transformed FL. For Part III expansion cohorts: a) DLBCL/transformed FL cohort: Patients with transformed FL are eligible, but they must be relapsed or refractory to standard treatments for transformed lymphoma. The Sponsor retains the option to limit the number of patients enrolled with transformed FL. Patients with Richter s transformation are not considered eligible for Part III. b) FL cohort: Grades 1-3a FL; MZL (splenic; nodal; extra-nodal) Please list the patients hematological malignancy Cell of origin for DLBCL, if known: ABC or GCB or neither Mutational Status Patient must have at least one measureable target lesion ( 1.5 cm) in its largest dimension by computerized tomography [CT] scan). Able to provide the most recent archival tumor tissue samples (formalin-fixed, paraffinembedded (FFPE blocks preferred; if not available, slides accepted). In the absence of sufficient archival tissue, a fresh biopsy from a safely accessible site, per Investigator determination and patient consent, will be allowed, providing the patient has more than one measurable target lesion and a biopsy consent form has been signed. o (Fresh) Biopsies obtained at any time between the last dose of the last prior cancer regimen and the Gpt (Day 7) are acceptable (Note: if fresh biopsy cannot be obtained, please contact the Medical Monitor). Please check where applicable. Archival tumor tissue sample submitted Fresh biopsy obtained & submitted Date of fresh biopsy (must be before Gpt) 7 ECOG performance status of 0 or 1.

2 8 Life expectancy (in the opinion of the Investigator) of 12 weeks. Site Number: birthdate: Screening number: page 2/6 Patients must meet the following criteria for study entry: Inclusion Criteria - Continued Note that if any box is marked NO, the patient is not eligible for enrollment. 9 Adverse events from prior anti-cancer therapy must have resolved to Grade Patients must have peripheral B-cell counts at or below 500 cells/l at screening. (Note: Post enrollment, CD19 B-cell counts must also be re-checked at C1/D1, i.e., within the 24-hour period before the first dose of RO (C1/D1). The Medical Monitor must be consulted if the peripheral B-cell count has not dropped to below 50 cells/l. Patients absolute (cells/microliter) peripheral B cell count (CD19) at screening Patients absolute (cells/microliter) T cell count: CD3 CD4 CD8 11 Adequate liver function: Total bilirubin 1.5 ULN. Patients with documented history of 12 Gilbert s Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 3 the ULN. Total bilirubin AST ALT Adequate hematological function: Neutrophil count of cells/l; Platelet count of 75,000/L (and platelet transfusion free within 14 days prior to administration of Gpt); Hemoglobin (Hb) 10.0 g/dl (6.2 mmol/l); transfusion free within 21 days prior to administration of Gpt. Note: Patients who do not meet the above hematologic criteria, due to bone marrow suppression from prior therapies and/or extensive tumor involvement in the marrow may be enrolled into the trial after consultation with the Medical Monitor. For patients who enter the study with monitor approved hematological indices that are below those defined above, please consult the medical monitor on the need for transfusion support within 21 days of Gpt. Note: specific platelet levels are required prior to administration of Gpt (i.e. 75,000/L) and RO at C1D1 as described in Section Neutrophil count Platelet count Hemoglobin 13 Adequate renal function: serum creatinine 1.5 ULN or a creatinine clearance (CrCl) calculated by Cockroft-Gault formula of 50 ml/min for patients in whom, in the Investigator s judgment, serum creatinine levels do not adequately reflect renal function. Serum creatinine Serum creatinine clearance 14 Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential who are considered to be post-menopausal ( 12 months of non-therapy amenorrhea) or surgically sterile (absence of

3 ovaries and/or uterus) are not required to have a pregnancy test Negative serologic or PCR test results for acute or chronic HBV infection. (Note: Patients whose HBV infection status cannot be determined by serologic test results [ must be negative for HBV by PCR to be eligible for study participation). Negative test results for Hepatitis C virus (HCV) and HIV. Note: Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation. Site Number: birthdate: Screening number: page 3/6 Patients must meet the following criteria for study entry: Inclusion Criteria - Continued Note that if any box is marked NO, the patient is not eligible for enrollment. 17 Patients must agree to either remain completely abstinent or to use two effective contraceptive methods that result in a failure rate of 1% per year from screening until (a) at least 3 months after pretreatment with obinutuzumab or 2 months after the last dose of RO , whichever is longer, if the patient is a male or (b) until at least 18 months after pretreatment with obinutuzumab o r 2 months after the last dose of RO , whichever is longer, if patient is a female. a) For women of childbearing potential, examples of contraceptive methods with a failure rate of 1% per year include: Tubal ligation, male sterilization, hormonal implants, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of < 1% per year. Barrier methods must always be supplemented with the use of a spermicide. b) For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for at least 3 months after last dose of obinutuzumab or 2 months after the last dose of RO (whichever is longer). Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 3 months after last dose of obinutuzumab or 2 months after the last dose of RO (whichever is longer) to avoid exposing the embryo. c) For both men and women, the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable

4 methods of contraception.

5 Site Number: birthdate: Screening number: page 4/6 Patients who meet any of the following criteria will be excluded from study entry: Exclusion Criteria Note that if any box is marked YES, the patient is not eligible for enrollment. 1 Inability to comply with protocol mandated hospitalization and restrictions. 2 Patients with CLL. Burkitt lymphoma and lymphoplasmacytic lymphoma. 3 Patients with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to Gpt infusion or by clinical judgment in the absence of a positive blood culture. Is the patient taking an antibiotic/antifungal agent with intent to treat? 4 Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, hepatitis B, hepatitis C, and HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing. 5 Pregnant or breast-feeding or intending to become pregnant during the study. 6 Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radioimmunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-ctla4, anti-pd1 and anti-pdl1) within 4 weeks or five half-lives of the drug, whichever is shorter, before Gpt infusion on C1/D-7. 7 History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows: Grade 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation 8 Documented refractoriness to an obinutuzumab-containing regimen Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent (defined as treatment for which there is currently no regulatory authority approved indication) within 4 weeks prior to Gpt infusion. Prior solid organ transplantation. Prior allogeneic SCT. 12 Autologous SCT within 100 days prior to Gpt infusion.

6 Site Number: birthdate: Screening number: page 5/6 Patients who meet any of the following criteria will be excluded from study entry: Exclusion Criteria - Continued Note that if any box is marked YES, the patient is not eligible for enrollment. 13 History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener s granulomatosis, Sjögren s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with a history of disease-related immune thrombocytopenic purpura or autoimmune hemolytic anemia may be eligible for this study. Patients with a history of Type I Diabetes Mellitus who are well controlled (defined as a screening Hemoglobin A1c 8% and no urinary ketoacidosis) are eligible. 14 History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins). Patient with history of confirmed progressive multifocal leukoencephalopathy (PML). Current or past history of CNS lymphoma Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Note: Patients with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits, as judged by the investigator, are allowed. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary disease) and known autoimmune diseases. Major surgery or significant traumatic injury 28 days prior to the Gpt infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment. Patients with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood for recurrence). 21 Significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina). 22 Administration of a live, attenuated vaccine within 4 weeks before Gpt infusion or anticipation that such a live attenuated vaccine will be required during the study. (Note: Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., Flumist ) at any time during the study treatment period.)

7 Site Number: birthdate: Screening number: page 6/6 Patients who meet any of the following criteria will be excluded from study entry: Exclusion Criteria - Continued Note that if any box is marked YES, the patient is not eligible for enrollment. 23 Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment 10 mg/day prednisone or equivalent within 2 weeks prior to Gpt infusion. Inhaled and topical steroids are permitted. History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator s judgment. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug. Finally, Investigators should review the vaccination status of potential study patients being considered for this study and follow local disease control and prevention guidelines for adult vaccination with any other non-live vaccines intended to prevent infectious disease prior to study. Will the patient participate in the trial? yes Date of consent dd mm yy no specify reason Date dd mm yy Authorized signature: