Locally Advanced and/ or Metastatic Solid Tumors MedDRA version: 17.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: CD40 receptor agonist
Product Code: Ro 700-9789/F01
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: RO7009789
Other de
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion 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 >/= 16 weeks - Adequate hematologic and end organ function - Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 - Ability to comply with the collection of tumor biopsies; tumors must be accessible for biopsy - Agreement to use effective methods of contraception per the protocol requirements; female patients of childbearing potential must have a negative pregnancy test (urine/serum) within seven days prior to the first study drug administration Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 95 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Diagnosis of non-small cell lung cancer (NSCLC) (excluded from Part I only) - 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, allowed: Palliative radiotherapy for bone metastases </= 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 allowed. Patients receiving denosumab prior to enrollment must be willing to receive a bisphosphonate while on study. - Uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent drainage procedures (at least one monthly). Patients 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 - Known primary CNS malignancy or symptomatic or untreated CNS metastases: patients with asymptomatic-treated CNS metastases may be enrolled after consultation with the Medical Monitor, provided they meet the following criteria: • Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNS-directed therapy and the screening radiographic study • No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1 Day 1 - Allergy or hypersensitivity to components of the RO7009789 formulation or to components of MPDL3280A formulation - History of autoimmune diseases - 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. - Patients with 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. Patients receiving prophylactic antibiotics are eligible. - 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 - Prior treatment with anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody - Previous treatment with any other compound that targets CD40 - Treatmen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part IA: - safety, tolerability of sequential single-dose (SD) RO7009789 intravenous (IV) and MPDL3280A (here: MPDL) - safety, tolerability of sequential SD RO7009789 subcutaneous (SC) and MPDL - single-agent MTD of RO7009789 SC - preferred route of sequential RO7009789 (IV vs SC) and MPDL - recommended SC dose of RO7009789 in combo with vaccines Part IB: - safety, tolerability of single combo of RO7009789 (IV and SC) and MPDL - MTD of RO7009789 (IV and SC) in combo with MPDL - recommended Part II dose of RO7009789 for multiple concomitant treatment with MPDL - preferred route (IV vs. SC) of RO7009789 in combo with MPDL Part II: - safety, tolerability of multiple administrations of RO7009789 (IV or SC) in combo with MPDL - optimal schedule of RO7009789 in combo with MPDL - Recommended Phase II Dose of RO7009789 for multiple combo treatment with MPDL Part III: - clinical activity of RO7009789 in combo with MPDL in tumor types identified in Part II;Secondary Objective: Parts IA,IB: -PK IV and SC RO7009789 SD (IA) and in combo with MPDL (IB) -PK MPDL after RO7009789 (IA) and in combo with RO7009789 (IB) -PD biomarkers of immune-modulatory and anti-tumor activity of RO7009789 SD (IA) and in combo with MPDL (IB) -PK/PD rel.ships of IV and SC RO7009789 SD (IA) and in combo with MPDL (IB) -immunogenic potential RO7009789 and/or MPDL by measuring ADA and assessing their relationship with other outcome measures (IA; IB) -clinical activity RO7009789 in combo with MPDL (IB) Parts II,III: -PK multiple dose (MD) RO7009789 in combo with MPDL (II; III) -PK MD MPDL in combo with RO7009789 (II; III) -PD biomarker of the immune-modulatory and anti-tumor activity of RO7009789 in combo with MPDL (II; III) -PK/PD rel.ships RO7009789 and MPDL in a MD setting (II; III) -immunogenic potential RO7009789 and/or MPDL by measuring ADA and assessing their relationship with other outcome measures (II; III) -clinical activity RO7009789 in combo with MPDL (II) ;Primary end point( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): c) Pharmacokinetic profile and parameters derived from the concentration-time curve following i.v. infusion of RO7009789 [AUC, Cmax, Cmin, CL, volume of distribution at steady state, half-life] (composite outcome measure) d) Pharmacokinetic profile and parameters derived from the concentration-time curve following s.c. administration of RO7009789 [AUC, Cmax, time to Cmax (Tmax), Cmin, apparent clearance CL/F, volume of distribution (V/F), t1/2] (composite outcome measure) e) Pharmacokinetic profile and and parameters derived from the concentration-time curve following i.v. or s.c. administration of RO7009789 [AUC, Cmax, Cmin, volume of distribution at steady state, half-life] (composite outcome measure) f) Pharmacokinetic profile and parameters derived from the concentration-time curve following IV infusion of MPDL3280A [Cmax, Cmin] (composite outcome measure) g) Pharmacodynamics: levels of circulating Ki67+ T-cell levels h) Pharmacodynamics: change in 18F-fluorothymidine (FLT) uptake by spleen i) Pharmacodynamics: change in CD8+ cells tumor-infiltration levels k) Pharmacodynamics: PD-L1 expression levels on tumor, immune-filtrating cells l) Efficacy [Best overall response rate, objective response rate, disease control rate, duration of objective response, progression-free survival] (composite outcome measure) m) Overall survival ;Timepoint(s) of evaluation of this end point: c) - Timeframe: 15 months d) - Timeframe: 15 months e) - Timeframe: 23 months (Part 2 and Part 3) f) - Timeframe: 36 months g) - Timeframe: 36 months h) - Timeframe: 15 months i) - Timeframe: 36 months k) - Timeframe: 36 months l) - Timeframe: 36 months m) - Timeframe: From first study treatment to death from any cause, approximately 36 months | — |
Countries
Canada, Denmark, France, Netherlands, Spain
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed