This study is currently recruiting participants.
Number
001578-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 3 Years Max Age: 100 Years
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Pregnant Women
Keywords
T cell immunoreceptor; Tumors with defects in SWI/SNF; Aggressive cancers
Recruitment Keyword(s)
None
Condition(s)
Medullary Carcinoma; Renal medullary carcinoma; SMARCA4; SMARCB1
Investigational Drug(s)
Tecentriq Tiragolumab
Investigational Device(s)
Intervention(s)
Drug: Atezolizumab Drug: Tiragolumab
Supporting Site
National Cancer Institute
Some cancers have tumor cells that lack specific genes, called SMARCB1 and SMARCA4. These types of cancer occur in children and young adults. These cancers are rare, but they are aggressive and hard to treat. Most people who get these cancers survive only months or years. Better treatments are needed.
Objective:
To test a drug (tiragolumab) alone and combined with a second drug (atezolizumab) to treat SMARCB1 and SMARCA4 deficient cancers.
Eligibility:
People aged 3 years or older with SMARCB1 or SMARCB4 deficient cancer. The cancer must have come back after treatment; failed to respond to treatment; or have no known standard treatment.
Design:
Participants will be screened.
Participants may get a central line. This is an opening into a large vein, usually in the chest, that stays in place for a long time. Blood samples can be taken from the central line, and drugs can be administered into it; that way, participants do not need to have a new needle inserted every time.
Treatment will be given in 21-day cycles. Both study drugs are given through a tube placed into a vein in the body. This will be done slowly over 1 hour or more. Participants will receive 1 or both drugs on the first day of each cycle.
Throughout the study, participants will have frequent blood and urine tests. They will have imaging scans and tests of their heart and lung function.
They may have blood and tissue samples stored for future research.
Participants may continue to receive treatment for up to 5 years.
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INCLUSION CRITERIA: 1. Age - Patients must be >= 12 months of age at the time of study enrollment. For Part A, patients must be <18 years old at enrollment. For Part B, there is no upper age limit. The Part B (Phase 2) cohorts will initially open concurrently with the Part A but will only enroll patients at least 18 years of age. Patients <18 years of age will be included in the Part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the Part A portion. 2. Diagnosis - Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional IHC or molecular confirmation of a pathologic tumor bi-allelic SMARCB1 (INI1) or SMARCA4 loss or mutation from a CLIA certified lab with the following disease histologies: A. Renal medullary carcinoma B. Malignant rhabdoid tumor (extra-CNS) C. Atypical teratoid rhabdoid tumor (CNS) D. Poorly differentiated chordoma E. Epithelioid sarcoma F. Other SMARCB1 or SMARCA4 deficient tumors Note: Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system 3. Disease Status - Part A: Patients must have either measurable or evaluable disease. Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors. 4. Therapeutic Options - Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life. 5. Performance Status - Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (Karnofsky/Lansky score of >= 50). Use Karnofsky for patients > 16 years of age and Lansky for patients <= 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. See https://www.cogmembers.org/site/pages/default.aspx?page=Prot_reference_materials under Standard Sections for Protocols. 6. Prior Therapy 6.1 Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately. 6.1.1 Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment. 6.1.1.1 >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/Tabl eOfMyelosuppressiveAnti-CancerAgents.pdf 6.1.2 Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or ANC counts): >= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment. 6.1.3 Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade <= 1. 6.1.4 Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. 6.1.5 Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) 6.1.6 Stem cell Infusions (with or without TBI): Autologous stem cell infusion including boost infusion: >= 30 days. 6.1.7 Cellular Therapy: >= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.). 6.1.8 XRT/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial BM radiation. 6.1.9 Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy. 6.1.10 Patients must not have had prior TIGIT targeting therapy. 6.1.11 Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti- PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co- inhibitory T cell receptor (i.e. OX-40, CD137). 6.1.12 Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment. 6.1.13 Patients must not be receiving concomitant systemic steroid medications and >= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions: -- The use of physiologic doses of corticosteroids (5 mg/m2/day up to 10 mg/day of prednisone equivalent) is acceptable. -- The use of topical, inhaled, or ophthalmic corticosteroids are acceptable. -- The use of acute, low-dose systemic immunosuppressant medication or a one- time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable 6.1.14 Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha [TNF-alpha] agents) must have concluded >= 14 days prior to study enrollment. 7. Organ Function Requirements 7.1 Adequate Bone Marrow Function Defined As: a. For patients with solid tumors without known bone marrow involvement -- Peripheral absolute neutrophil count (ANC) >= 1000/uL -- Platelet count >= 100,000/uL(transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) b. Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in section 7.1 above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. 7.2 Adequate Renal Function Defined As: -- A creatinine based on age/gender as follows: 1 to < 2 years: 0.6 [Male] 0.6 [Female] 2 to < 6 years<TAB>: 0.8 [Male] 0.8 [Female] 6 to < 10 years: 1 [Male] 1 [Female] 10 to < 13 years: 1.2<TAB> [Male] 1.2 [Female] 13 to < 16 years: 1.5 [Male] 1.4 [Female] >= 16 years: 1.7 [Male] 1.4 [Female] The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC. OR - a 24 hour urine Creatinine clearance >= 70 mL/min/1.73 m2 OR - a GFR >= 70 mL/min/1.73 m2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard). Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility. 7.3 Adequate Liver Function Defined As: - Bilirubin (sum of conjugated + unconjugated or total) <= 1.5 x upper limit of normal (ULN) for age -- Patients with known Gilbert disease: total bilirubin <= 3 x ULN - SGPT (ALT) <= 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L - Albumin >= 2 g/dL 7.4 Adequate Neurologic Function Defined As: -- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days. -- Nervous system disorders (CTCAE v5) resulting from prior therapy must be <= Grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible. 7.5 Adequate Coagulation Defined As: -- INR <= 1.5 7.6 Adequate Pancreatic Function Defined As: -- Serum amylase <= 1.5xULN -- Serum lipase <= 1.5xULN 7.7 Adequate Calcium Regulation Defined As: -- Grade 1 or lower calcium level -- Note: can have history of hypercalcemia as long as controlled and asymptomatic EXCLUSION CRITERIA 1. Pregnancy or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control. It is not known if atezolizumab or tirgolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later. 2. Concomitant Medications 2.1 Corticosteroids 2.2 Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. 2.3 Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible. 2.4 Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible. 3. Study Specific 3.1 Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection. 3.2 History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins 3.3 Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation 3.4 Patients who have undergone allogeneic bone marrow or stem cell transplant are not eligible. 3.5 Patients with known, untreated CNS metastases will be excluded with the following exceptions: -- Patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows no evidence for active disease in the CNS. 3.6 Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible. 3.7 Patients who have active immune deficiency are not eligible. 3.8 Patients who have known active tuberculosis are not eligible. 3.9 Hepatitis B or C infection: a. Patients <18 years old at enrollment, who have known hepatitis B or C b.Patients >=18 years old at enrollment with: i. Positive hepatitis B surface antigen (HBsAg), OR ii. Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) DNA >=500 IU/mL, OR iii. Positive hepatitis C virus (HCV) antibody with a positive HCV RNA test Note: For adults (>=18 years old at enrollment), Hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (>=18 years old at enrollment), Hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test. 3.10 Patients who have a known, recent EBV infection or known history of chronic, active infection are not eligible. 3.11 Patients who have history of or active HIV are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count >= 200/uL, and have an undetectable viral load. 3.12 Patients who have significant cardiovascular disease (such as New York Heart Association Class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible. 3.13 Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible. 3.14 Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted. 3.15 Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX(R)) are allowed. 4. Infection: Patients who have an uncontrolled infection are not eligible. 5. Patients who have received a prior solid organ transplantation are not eligible. 6. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
1. Age - Patients must be >= 12 months of age at the time of study enrollment. For Part A, patients must be <18 years old at enrollment. For Part B, there is no upper age limit. The Part B (Phase 2) cohorts will initially open concurrently with the Part A but will only enroll patients at least 18 years of age. Patients <18 years of age will be included in the Part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the Part A portion.
2. Diagnosis - Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional IHC or molecular confirmation of a pathologic tumor bi-allelic SMARCB1 (INI1) or SMARCA4 loss or mutation from a CLIA certified lab with the following disease histologies:
A. Renal medullary carcinoma
B. Malignant rhabdoid tumor (extra-CNS)
C. Atypical teratoid rhabdoid tumor (CNS)
D. Poorly differentiated chordoma
E. Epithelioid sarcoma
F. Other SMARCB1 or SMARCA4 deficient tumors
Note: Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
3. Disease Status - Part A: Patients must have either measurable or evaluable disease. Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors.
4. Therapeutic Options - Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
5. Performance Status - Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (Karnofsky/Lansky score of >= 50). Use Karnofsky for patients > 16 years of age and Lansky for patients <= 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
See https://www.cogmembers.org/site/pages/default.aspx?page=Prot_reference_materials under Standard Sections for Protocols.
6. Prior Therapy
6.1 Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
6.1.1 Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
6.1.1.1 >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/Tabl eOfMyelosuppressiveAnti-CancerAgents.pdf
6.1.2 Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or ANC counts): >= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
6.1.3 Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade <= 1.
6.1.4 Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
6.1.5 Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors)
6.1.6 Stem cell Infusions (with or without TBI): Autologous stem cell infusion including boost infusion: >= 30 days.
6.1.7 Cellular Therapy: >= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.).
6.1.8 XRT/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial BM radiation.
6.1.9 Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy.
6.1.10 Patients must not have had prior TIGIT targeting therapy.
6.1.11 Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti- PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co- inhibitory T cell receptor (i.e. OX-40, CD137).
6.1.12 Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment.
6.1.13 Patients must not be receiving concomitant systemic steroid medications and >= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
-- The use of physiologic doses of corticosteroids (5 mg/m2/day up to 10 mg/day of prednisone equivalent) is acceptable.
-- The use of topical, inhaled, or ophthalmic corticosteroids are acceptable.
-- The use of acute, low-dose systemic immunosuppressant medication or a one- time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
6.1.14 Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha [TNF-alpha] agents) must have concluded >= 14 days prior to study enrollment.
7. Organ Function Requirements
7.1 Adequate Bone Marrow Function Defined As:
a. For patients with solid tumors without known bone marrow involvement
-- Peripheral absolute neutrophil count (ANC) >= 1000/uL
-- Platelet count >= 100,000/uL(transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
b. Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in section 7.1 above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity.
7.2 Adequate Renal Function Defined As:
-- A creatinine based on age/gender as follows:
1 to < 2 years: 0.6 [Male] 0.6 [Female]
2 to < 6 years<TAB>: 0.8 [Male] 0.8 [Female]
6 to < 10 years: 1 [Male] 1 [Female]
10 to < 13 years: 1.2<TAB> [Male] 1.2 [Female]
13 to < 16 years: 1.5 [Male] 1.4 [Female]
>= 16 years: 1.7 [Male] 1.4 [Female]
The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.
OR - a 24 hour urine Creatinine clearance >= 70 mL/min/1.73 m2
OR - a GFR >= 70 mL/min/1.73 m2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
7.3 Adequate Liver Function Defined As:
- Bilirubin (sum of conjugated + unconjugated or total) <= 1.5 x upper limit of normal (ULN) for age
-- Patients with known Gilbert disease: total bilirubin <= 3 x ULN
- SGPT (ALT) <= 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
- Albumin >= 2 g/dL
7.4 Adequate Neurologic Function Defined As:
-- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days.
-- Nervous system disorders (CTCAE v5) resulting from prior therapy must be <= Grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible.
7.5 Adequate Coagulation Defined As:
-- INR <= 1.5
7.6 Adequate Pancreatic Function Defined As:
-- Serum amylase <= 1.5xULN
-- Serum lipase <= 1.5xULN
7.7 Adequate Calcium Regulation Defined As:
-- Grade 1 or lower calcium level
-- Note: can have history of hypercalcemia as long as controlled and asymptomatic
EXCLUSION CRITERIA
1. Pregnancy or Breast-Feeding
Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
It is not known if atezolizumab or tirgolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later.
2. Concomitant Medications
2.1 Corticosteroids
2.2 Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
2.3 Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.
2.4 Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible.
3. Study Specific
3.1 Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection.
3.2 History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
3.3 Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
3.4 Patients who have undergone allogeneic bone marrow or stem cell transplant are not eligible.
3.5 Patients with known, untreated CNS metastases will be excluded with the following exceptions:
-- Patients with a history of CNS metastases that have been previously treated may enroll if sequential imaging shows no evidence for active disease in the CNS.
3.6 Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible.
3.7 Patients who have active immune deficiency are not eligible.
3.8 Patients who have known active tuberculosis are not eligible.
3.9 Hepatitis B or C infection:
a. Patients <18 years old at enrollment, who have known hepatitis B or C
b.Patients >=18 years old at enrollment with:
i. Positive hepatitis B surface antigen (HBsAg), OR
ii. Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) DNA >=500 IU/mL, OR
iii. Positive hepatitis C virus (HCV) antibody with a positive HCV RNA test
Note: For adults (>=18 years old at enrollment), Hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (>=18 years old at enrollment), Hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test.
3.10 Patients who have a known, recent EBV infection or known history of chronic, active infection are not eligible.
3.11 Patients who have history of or active HIV are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count >= 200/uL, and have an undetectable viral load.
3.12 Patients who have significant cardiovascular disease (such as New York Heart Association Class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible.
3.13 Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible.
3.14 Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted.
3.15 Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX(R)) are allowed.
4. Infection: Patients who have an uncontrolled infection are not eligible.
5. Patients who have received a prior solid organ transplantation are not eligible.
6. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
Principal Investigator
Referral Contact
For more information: