Clinical Trials /

A Study of Selicrelumab (RO7009789) in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Solid Tumors

NCT02304393

Description:

This is an open-label, multicenter study designed to assess the safety, pharmacokinetics, pharmacodynamics and activity of Selicrelumab administered in combination with Atezolizumab (ATZ) in participants with metastatic or locally advanced solid tumors. The study will be conducted in two Parts (I and II), with Part I divided into Parts IA and IB. All participants will be followed up for survival until death or loss of follow-up after the last visit or withdrawal of consent.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Selicrelumab (RO7009789) in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Solid Tumors
  • Official Title: An Open-Label, Multicenter, Dose-Escalation Phase IB Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Therapeutic Activity of RO7009789 (CD40 Agonist) in Combination With Atezolizumab (Anti PD-L1) in Patients With Locally Advanced and/or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BP29392
  • SECONDARY ID: 2014-002835-32
  • NCT ID: NCT02304393

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
AtezolizumabMPDL3280A, TecentriqPart IA: Selicrelumab (IV) + Atezolizumab
SelicrelumabRO7009789Part IA: Selicrelumab (IV) + Atezolizumab

Purpose

This is an open-label, multicenter study designed to assess the safety, pharmacokinetics, pharmacodynamics and activity of Selicrelumab administered in combination with atezolizumab (ATZ) in participants with metastatic or locally advanced solid tumors. The study will be conducted in two Parts (I and II), with Part I divided into Parts IA and IB. All participants will be followed up for survival until death or loss of follow-up after the last visit or withdrawal of consent.

Trial Arms

NameTypeDescriptionInterventions
Part IA: Selicrelumab (IV) + AtezolizumabExperimentalSelicrelumab at a dose of 16 milligrams (mg) will be administered intravenously (IV) on Day 1 of Cycle 1 (first cycle in this group was of 42 days, and subsequent 21-day cycles); and atezolizumab 1200 mg will be administered IV after 6 weeks on Day 1 of Cycle 2, followed by every 3 weeks during Part IA until disease progression, death, loss of follow-up, or withdrawal of consent.
  • Atezolizumab
  • Selicrelumab
Part IA: Selicrelumab(SC) + AtezolizumabExperimentalSelicrelumab at a starting dose of 1 mg will be administered subcutaneously (SC) on Day 1 of Cycle 1 (21-day cycle) which will follow escalation in sequential cohorts; and atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 2, and followed by every 3 weeks during Part IA as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity.
  • Atezolizumab
  • Selicrelumab
Part IB: Selicrelumab + AtezolizumabExperimentalSelicrelumab will be administered at a starting dose of 1 mg SC or at 50 percent (%) of the SC MTD (but not more than 4 mg) IV on Day 2 of Cycle 1 (21-day cycle) which will follow escalation in sequential cohorts; and atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 1, and followed by every 3 weeks during Part IB as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity.
  • Atezolizumab
  • Selicrelumab
Part II: Selicrelumab + AtezolizumabExperimentalAtezolizumab 1200 mg will be administered IV on Day 1 of Cycle 1, and followed by every 3 weeks; and Selicrelumab will be administered at the dose defined in Part IB (not exceeding 80 mg SC [unless IV administration in Part IB demonstrates better benefit/risk ratio]) on Day 2 (1 day after atezolizumab administration) of every second cycle from Cycles 1 to 7, and every fourth cycle thereafter during Part II as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity.
  • Atezolizumab
  • Selicrelumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors,
             which are not amenable to standard therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy greater than or equal to (>/=) 16 weeks

          -  Adequate hematologic and end organ function

          -  Measurable disease per RECIST Version 1.1

          -  Ability to comply with the protocol requirements

          -  Female participants of childbearing potential must have a negative pregnancy test
             (urine/serum) within seven days prior to the first study drug administration

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods that result in a failure rate
             of less than (<) 1% per year during the treatment period and for at least 5 months
             after the last dose of study treatment

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures, and agreement to refrain from donating sperm during the
             treatment period and for at least 28 days after the last dose of study treatment

        Exclusion Criteria:

          -  If one of the following laboratory results obtained within 14 days prior to the first
             study treatment (Cycle 1 Day 1) are: soluble interleukin 2 receptor (sCD25) greater
             than (>) 2 × upper limit of normal (ULN); Serum ferritin >1000 nanograms per
             milliliter (ng/mL)

          -  Any approved anti-cancer therapy that includes chemotherapy, hormonal therapy, or
             radiotherapy within 2 weeks prior to the first dose of study treatment; the following
             is, however, allowed: Palliative radiotherapy for bone metastases less than or equal
             to (</=) 2 weeks prior to Cycle 1 Day 1

          -  Adverse events from prior anti-cancer therapy that have not resolved to Grade </= 1
             except for any grade alopecia and </= Grade 2 peripheral neuropathy

          -  Bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy
             for other reasons (example: bone metastasis or osteoporosis) is allowed

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent
             drainage procedures (one monthly or more frequently). Participants with indwelling
             catheters are allowed

          -  Known clinically significant liver disease which includes active viral, alcoholic, or
             other hepatitis, cirrhosis, fatty liver, and inherited liver disease

          -  History (within the previous year) of congestive heart failure, stroke, arrhythmia, or
             myocardial infarction

          -  History of peripheral venous thrombosis or thromboembolic event (within 12 months
             prior to Cycle 1 Day 1)

          -  Significant cardio- or cerebrovascular disease within 6 months prior to Cycle 1 Day 1

          -  Known hereditary or acquired coagulopathies

          -  Clinically meaningful proteinuria

          -  Requiring dialysis (peritoneal or hemodialysis)

          -  Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS
             metastases: participants with asymptomatic-treated CNS metastases may be enrolled
             after consultation with the Medical Monitor, provided they meet the following
             criteria:

               1. Radiographic demonstration of improvement upon completion of CNS-directed therapy
                  and no evidence of interim progression between the completion of CNS-directed
                  therapy and the screening radiographic study

               2. No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle
                  1 Day 1

          -  Pregnancy, lactation, or breastfeeding

          -  Allergy or hypersensitivity to components of the RO7009789 formulation or to
             components of atezolizumab formulation

          -  History of autoimmune diseases (participants with a history of autoimmune
             hypothyroidism on a stable dose of thyroid replacement hormone may be eligible;
             participants with controlled Type 1 diabetes mellitus on a stable insulin regimen may
             be eligible for this study)

          -  History of idiopathic pulmonary fibrosis, pneumonitis (excluding infectious
             disease-induced), organizing pneumonia, or evidence of active pneumonitis

          -  History of radiation pneumonitis in the radiation field (fibrosis) is permitted

          -  Participants with human immunodeficiency virus (HIV) infection, active hepatitis B
             (chronic or acute), or hepatitis C infection

          -  Active tuberculosis

          -  Severe infections within 4 weeks prior to Cycle 1 Day 1

          -  Signs or symptoms of infection within 2 weeks prior to Cycle 1 Day 1

          -  Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1

          -  Major surgical procedure within 28 days prior to Cycle 1 Day 1 or anticipation of need
             for a major surgical procedure during the course of the study

          -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 or
             anticipation that such a live attenuated vaccine will be required during the study

          -  Malignancies other than disease under study within 3 years prior to Cycle 1 Day 1 with
             the exception of those with a negligible risk of metastasis or death and with expected
             curative outcome

          -  Previous treatment with any other compound that targets cluster of differentiation 40
             (CD40) (like Chi Lob 7/4 and ADC1013)

          -  Treatment with systemic immunostimulatory agents (including but not limited to
             interferon (IFN)-alpha, Interleukin-2 (IL-2) within 4 weeks or 5 times the half-life
             of the drug, whichever is shorter, prior to Cycle 1 Day 1

          -  Treatment with investigational agent within 4 weeks prior to Cycle 1 Day 1 (or within
             5 times the half-life of the investigational product, whichever is longer)

          -  Concomitant treatment with anticoagulants (example: coumadin, heparin) except low dose
             molecular weight heparin for prophylactic purposes and direct factor Xa inhibitors

          -  Treatment with systemic immunosuppressive medications (including but not limited to
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
             necrosis factor (TNF) agent within 2 weeks prior to Cycle 1 Day 1

               1. Participants who have received acute, low-dose, systemic immunosuppressant
                  medications (example: a one-time dose of dexamethasone for nausea) may be
                  enrolled in the study after discussion with and approval by the Medical Monitor

               2. The use of corticosteroids as premedication in case of dye allergy previous to
                  computed tomography (CT) scan is allowed

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Participants with prior allogeneic bone marrow transplantation or prior solid organ
             transplantation

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the participants at high risk from treatment
             complications
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events and Serious Adverse Events
Time Frame:Baseline up to 28 days after the last dose (approximately 38 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part IA: Area Under the Concentration Time Curve (AUC) of Selicrelumab
Time Frame:Pre Selicrelumab dose (1hour[Hr]) on Cycle(Cy)1 Day1(D1); 4,8,24,48,72Hr post D1dose; D8,15 of Cy1; D1 Cy2&3 (10 minutes pre ATZ dose); at radiographic disease progression (PD)(up to 38 months);28&150 days after last ATZ dose (up to38months)(Cy=21days)
Safety Issue:
Description:
Measure:Part IA: Maximum Serum Concentration (Cmax) of Selicrelumab
Time Frame:Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 minutes [min] pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part IA: Time to Cmax (Tmax) of Selicrelumab
Time Frame:Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part IA: Minimum Serum Concentration Under Steady-State (Cmin) of Selicrelumab
Time Frame:Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part IA: Apparent Clearance (CL/F) of Selicrelumab
Time Frame:Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part IA: Half-Life (t1/2) of Selicrelumab
Time Frame:Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part IA: Cmax of Atezolizumab
Time Frame:Pre ATZ (within 10 min) & at end of 60 min ATZ infusion on Cy2D1; pre ATZ dose (within 10 min) on D1 of Cy3,4,5,9,& every 8Cy thereafter(up to 38 months); at radiographic PD(up to 38 months); 28&150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IA: Cmin of Atezolizumab
Time Frame:Pre ATZ (within 10 min) & at end of 60 min ATZ infusion on Cy2D1; pre ATZ dose (within 10 min) on D1 of Cy3,4,5,9,& every 8Cy thereafter(up to 38 months); at radiographic PD(up to 38 months); 28&150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: AUC of SC Selicrelumab
Time Frame:Pre ATZ dose (within 1 Hr) on Cy1D1, Pre Selicrelumab dose (within 1 Hr) on Cy1D2; Cy1 D3,4,5,9,15 post D2 dose; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: Cmax of SC Selicrelumab
Time Frame:Pre ATZ dose (within 1 Hr) on Cy1D1, Pre Selicrelumab dose (within 1 Hr) on Cy1D2; Cy1 D3,4,5,9,15 post D2 dose; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: Tmax of SC Selicrelumab
Time Frame:Pre ATZ dose (within 1 Hr) on Cy1D1, Pre Selicrelumab dose (within 1 Hr) on Cy1D2; Cy1 D3,4,5,9,15 post D2 dose; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: Cmin of SC Selicrelumab
Time Frame:Pre ATZ dose (within 1 Hr) on Cy1D1, Pre Selicrelumab dose (within 1 Hr) on Cy1D2; Cy1 D3,4,5,9,15 post D2 dose; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: CL/F of SC Selicrelumab
Time Frame:Pre ATZ dose (within 1 Hr) on Cy1D1, Pre Selicrelumab dose (within 1 Hr) on Cy1D2; Cy1 D3,4,5,9,15 post D2 dose; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: Apparent Volume of Distribution (V/F) of SC Selicrelumab
Time Frame:Pre ATZ dose (within 1 Hr) on Cy1D1, Pre Selicrelumab dose (within 1 Hr) on Cy1D2; Cy1 D3,4,5,9,15 post D2 dose; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: t1/2 of SC Selicrelumab
Time Frame:Pre ATZ dose (within 1 Hr) on Cy1D1, Pre Selicrelumab dose (within 1 Hr) on Cy1D2; Cy1 D3,4,5,9,15 post D2 dose; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: Cmax of Atezolizumab
Time Frame:Pre ATZ (within 1 Hr) & at end of 60 min ATZ infusion on Cy1D1; pre ATZ dose (within 10 min) on D1 of Cy2,3,4,8,& every 8Cy thereafter (up to 38 months); at radiographic PD (up to 38 months); 28&150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IB: Cmin of Atezolizumab
Time Frame:Pre ATZ (within 1 Hr) & at end of 60 min ATZ infusion on Cy1D1; pre ATZ dose (within 10 min) on D1 of Cy2,3,4,8,& every 8Cy thereafter (up to 38 months); at radiographic PD (up to 38 months); 28&150 days after last ATZ dose (up to 38 months) (Cy=21 days)
Safety Issue:
Description:
Measure:Part II: AUC of Selicrelumab
Time Frame:Pre Selicrelumab (within 1Hr) on Cy1D2; Cy1,5D5,8,15; pre ATZ (10 min) on D1-Cy2,4,6,8 and thereafter except Cy 11, 15, 19; pre Selicrelumab(10 min) on D2 of Cy3,5,11,15,19; D8 of Cy11,15,19; 28&150 days after last ATZ (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: Cmax of Selicrelumab
Time Frame:Pre Selicrelumab (within 1Hr) on Cy1D2; Cy1, 5D5, 8, 15; pre ATZ (10 min) on D1-Cy2,4,6,8 and thereafter except Cy 11, 15, 19; pre Selicrelumab(10 min) on D2-Cy3,5,11,15,19; D8-Cy 11,15,19; 28&150 days after last ATZ (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: Tmax of Selicrelumab
Time Frame:Pre Selicrelumab (within 1Hr) on Cy1D2; Cy 1, 5 D5,8,15; pre ATZ (10 min) on D1-Cy2,4,6,8 and thereafter except Cy 11, 15, 19; pre Selicrelumab(10 min) on D2 of Cy3,5,11,15,19; D8 of Cy 11,15,19; 28&150 days after last ATZ (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: Cmin of Selicrelumab
Time Frame:Pre Selicrelumab (within 1Hr) on Cy1D2; Cy1,5D5, 8,15; pre ATZ (10 min) on D1-Cy2,4,6,8 and thereafter except Cy11, 15, 19; pre Selicrelumab(10 min) on D2-Cy3,5,11,15,19; D8-Cy 11,15,19; 28&150 days after last ATZ (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: CL/F of Selicrelumab
Time Frame:Pre Selicrelumab (within 1Hr) on Cy1D2; Cy1,5D5,8,15; pre ATZ (10 min) on D1-Cy2,4,6,8 and thereafter except Cy 11, 15, 19; pre Selicrelumab(10 min) on D2-Cy3,5,11,15,19; D8-Cy11,15,19; 28&150 days after last ATZ (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: V/F of Selicrelumab
Time Frame:Pre Selicrelumab (within 1Hr) on Cy1D2; Cy 1,5D5,8,15; pre ATZ (10 min) on D1-Cy2,4,6,8 and thereafter except Cy 11, 15, 19; pre Selicrelumab(10 min) on D2-Cy3,5,11,15,19; D8-Cy 11,15,19; 28&150 days after last ATZ (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: t1/2 of Selicrelumab
Time Frame:Pre Selicrelumab (within 1Hr) on Cy1D2; Cy1,5D5,8,15; pre ATZ (10 min) on D1-Cy2,4,6,8 and thereafter except Cy 11, 15, 19; pre Selicrelumab(10 min) on D2-Cy3,5,11,15,19; D8-Cy 11,15,19; 28&150 days after last ATZ (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: Cmax of Atezolizumab
Time Frame:Cy1D1: pre ATZ dose (within 1 Hr), at end of ATZ infusion (60 min infusion); pre-ATZ dose (within 10 min)on D1 Cy2, 3, 4, 5, 6, 8, and thereafter (up to 38 months); 28 and 150 days after last ATZ dose (up to 38 months) (Cy = 21 days)
Safety Issue:
Description:
Measure:Part II: Cmin of Atezolizumab
Time Frame:Cy1D1: pre ATZ dose (within 1 Hr), at end of ATZ infusion (60 min infusion); pre-ATZ dose (within 10 min)on D1 Cy2, 3, 4, 5, 6, 8, and thereafter (up to 38 months); 28 and 150 days after last ATZ dose (up to 38 months) (Cy = 21 days)
Safety Issue:
Description:
Measure:Part II: Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Percentage of Participants With Best Overall Response, as Determined by Investigator Using Unidimensional Immune-Related Response Criteria (irRC)
Time Frame:Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Percentage of Participants With Disease Control, as Determined by Investigator Using RECIST Version 1.1
Time Frame:Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Percentage of Participants With Disease Control, as Determined by Investigator Using Unidimensional irRC
Time Frame:Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Duration of Objective Response, as Determined by Investigator Using RECIST Version 1.1
Time Frame:First occurrence of response up to relapse or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Duration of Objective Response, as Determined by Investigator Using Unidimensional irRC
Time Frame:First occurrence of response up to relapse or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Progression-Free Survival (PFS), as Determined by Investigator Using RECIST Version 1.1
Time Frame:Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Overall Survival
Time Frame:Baseline up to death due to any cause (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part IA, IB, and II: Percentage of Participants With Auto-antibodies
Time Frame:Pre Selicrelumab dose(within 1 Hr) on Cy1D1;pre ATZ dose(within 10 min) on D1 Cy2,3,4,5 and every 8 cycles thereafter, up to 38 months); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months overall) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IA, IB, and II: Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Selicrelumab
Time Frame:Pre Selicrelumab dose(within 1 Hr) on Cy1D1;pre ATZ dose(within 10 min) on D1 Cy2,3,4,5 and every 8 cycles thereafter, up to 38 months); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months overall) (Cy=21 days)
Safety Issue:
Description:
Measure:Part IA, IB, and II: Percentage of Participants With ATA to ATZ
Time Frame:Pre ATZ(within 10 min)on D1 Cy2,3,4,5(Part IA),9(Cy8 for Part II)& every 8 cycles thereafter(up to 38 months);pre ATZ(within 1Hr) on Cy1D1(for Part IB & II);at radiographic PD(up to 38 months),28&150 days after last ATZ dose(up to 38 months)(Cy=21 days)
Safety Issue:
Description:
Measure:Part IA: Levels of Circulating Rabbit Polyclonal Antibody (Ki67) T Cells Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Pre Selicrelumab (within 1 Hr) & 72, 192,360 Hr post Cy1 D1 dose; pre ATZ (within 10 min) & 48,192 Hr post dose on Cy2 D1; pre ATZ (within 10 min) & 192 Hr post Cy3 D1 dose; at radiographic tumor regression/PD (up to 38 months) (Cy= 21 days)
Safety Issue:
Description:
Measure:Part IB: Levels of Circulating Ki67 T Cells Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Pre ATZ (within 1 Hr) on Cy 1 D1; Cy1 D4, 9, 15; pre ATZ (within 10 min) on Cy2 D1; Cy2 D8; pre ATZ (within 10 min) on Cy4 D1 onwards; at radiographic tumor regression/PD (up to 38 months) (Cy = 21 days)
Safety Issue:
Description:
Measure:Part II: Levels of Circulating Ki67 T Cells Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Part II: Pre ATZ (within 1 Hr) Cy1, 6, 11, 15, 19 D1; Cy1 D8, 15; pre ATZ (within 10 min) Cy2, 3, 4, 5 D1; Cy3, 5, 11, 15, 19 D8; Cy 5 D15; 28 days after last ATZ dose(up to 38 months); at radiographic tumor regression/PD (up to 38 months) (Cy= 21 days)
Safety Issue:
Description:
Measure:Part IA: Levels of Cluster of Differentiation 8 (CD8+) Cells Tumor-Infiltration Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Pre Selicrelumab (within 1 Hr) & 72, 192,360 Hr post Cy1 D1 dose; pre ATZ (within 10 min) & 48,192 Hr post dose on Cy2 D1; pre ATZ (within 10 min) & 192 Hr post Cy3 D1 dose; at radiographic tumor regression/PD (up to 38 months) (Cy= 21 days)
Safety Issue:
Description:
Measure:Part IB: Levels of CD8+ Cells Tumor-Infiltration Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Pre ATZ (within 1 Hr) on Cy 1 D1; Cy1 D4, 9, 15; pre ATZ (within 10 min) on Cy2 D1; Cy2 D8; pre ATZ (within 10 min) on Cy4 D1 onwards; at radiographic tumor regression/PD (up to 38 months) (Cy = 21 days)
Safety Issue:
Description:
Measure:Part IA: Levels of Programmed Death Ligand 1 (PD-L1) Expression on Both Tumor and Immune-Infiltrating Cells Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Pre Selicrelumab (within 1 Hr) & 72, 192,360 Hr post Cy1 D1 dose; pre ATZ (within 10 min) & 48,192 Hr post dose on Cy2 D1; pre ATZ (within 10 min) & 192 Hr post Cy3 D1 dose; at radiographic tumor regression/PD (up to 38 months) (Cy= 21 days)
Safety Issue:
Description:
Measure:Part IB: Levels of PD-L1 Expression on Both Tumor and Immune-Infiltrating Cells Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Pre ATZ (within 1 Hr) on Cy 1 D1; Cy1 D4, 9, 15; pre ATZ (within 10 min) on Cy2 D1; Cy2 D8; pre ATZ (within 10 min) on Cy4 D1 onwards; at radiographic tumor regression/PD (up to 38 months) (Cy = 21 days)
Safety Issue:
Description:
Measure:Part II: Levels of PD-L1 Expression on Both Tumor and Immune-Infiltrating Cells Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Part II: Pre ATZ (within 1 Hr) Cy1, 6, 11, 15, 19 D1; Cy1 D8, 15; pre ATZ (within 10 min) Cy2, 3, 4, 5 D1; Cy3, 5, 11, 15, 19 D8; Cy 5 D15; 28 days after last ATZ dose(up to 38 months); at radiographic tumor regression/PD (up to 38 months) (Cy= 21 days)
Safety Issue:
Description:
Measure:Part IA: V/F of Selicrelumab
Time Frame:Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)
Safety Issue:
Description:
Measure:Part II: PFS, as Determined by Investigator Using Unidimensional irRC
Time Frame:Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)
Safety Issue:
Description:
Measure:Part II: Levels of CD8+ Cells Tumor-Infiltration Assessed by Immunophenotyping by Flow Cytometry
Time Frame:Part II: Pre ATZ (within 1 Hr) Cy1, 6, 11, 15, 19 D1; Cy1 D8, 15; pre ATZ (within 10 min) Cy2, 3, 4, 5 D1; Cy3, 5, 11, 15, 19 D8; Cy 5 D15; 28 days after last ATZ dose(up to 38 months); at radiographic tumor regression/PD (up to 38 months) (Cy= 21 days)
Safety Issue:
Description:
Measure:Part IB: AUC of IV Selicrelumab
Time Frame:Pre ATZ(1 Hr) Cy1D1,2;end of 30-min Selicrelumab infusion,0.25,2,4,6,8,10Hr post infusion start Cy1D2;24,30-36,48,72Hr Post Cy1D2 dose;Cy 1D9;D1 Cy2,3(10min pre ATZ);at radiographic PD(up to 38mon);28&150days after last ATZ dose(up to38mon)(Cy=21days)
Safety Issue:
Description:
Measure:Part IB: Cmax of IV Selicrelumab
Time Frame:Pre ATZ(1 Hr)Cy1D1,2;end of 30-min Selicrelumab infusion,0.25,2,4,6,8,10Hr post infusion start Cy1D2;24,30-36,48,72Hr Post Cy1D2 dose;Cy 1D9;D1 Cy2,3(10min pre ATZ);at radiographic PD(up to 38mon);28&150days after last ATZ dose(up to38mont)(Cy=21days)
Safety Issue:
Description:
Measure:Part IB: Cmin of IV Selicrelumab
Time Frame:Pre ATZ(1 Hr) Cy1D1,2;end of 30-min Selicrelumab infusion,0.25,2,4,6,8,10Hr post infusion start Cy1D2;24,30-36,48,72Hr Post Cy1D2 dose;Cy 1D9;D1 Cy2,3(10min pre ATZ);at radiographic PD(up to 38mon);28&150days after last ATZ dose(up to38mon)(Cy=21days)
Safety Issue:
Description:
Measure:Part IB: Total Clearance (CL) of IV Selicrelumab
Time Frame:Pre ATZ(1 Hr) Cy1D1,2;end of 30-min Selicrelumab infusion,0.25,2,4,6,8,10Hr post infusion start Cy1D2;24,30-36,48,72Hr Post Cy1D2 dose;Cy 1D9;D1 Cy2,3(10min pre ATZ);at radiographic PD(up to 38mon);28&150days after last ATZ dose(up to38mon)(Cy=21days)
Safety Issue:
Description:
Measure:Part IB: Volume of Distribution (Vss) of IV Selicrelumab
Time Frame:Pre ATZ(1 Hr) Cy1D1,2;end of 30-min Selicrelumab infusion,0.25,2,4,6,8,10Hr post infusion start Cy1D2;24,30-36,48,72Hr Post Cy1D2 dose;Cy 1D9;D1 Cy2,3(10min pre ATZ);at radiographic PD(up to 38mon);28&150days after last ATZ dose(up to38mon)(Cy=21days)
Safety Issue:
Description:
Measure:Part IB: t1/2 of IV Selicrelumab
Time Frame:Pre ATZ(1 Hr) Cy1D1,2;end of 30-min Selicrelumab infusion,0.25,2,4,6,8,10Hr post infusion start Cy1D2;24,30-36,48,72Hr Post Cy1D2 dose;Cy 1D9;D1 Cy2,3(10min pre ATZ);at radiographic PD(up to 38mon);28&150days after last ATZ dose(up to38mon)(Cy=21days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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