Colorectal Cancer, Non-small Cell Lung Cancer, Ovarian Neoplasms, Pancreatic Adenocarcinoma, Renal Cell Carcinoma
Conditions
Keywords
HLA-G, Human leukocyte antigen G, Renal cell carcinoma, Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal cancer, Epithelial ovarian cancer, Primary peritoneal cancer, Fallopian tube cancer, RO7515629, Tocilizumab
Brief summary
The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, immune response and preliminary anti-tumor activity of RO7515629 alone in participants with advanced or metastatic solid tumors expressing human leukocyte antigen G (HLA-G).
Interventions
DRUGRO7515629
RO7515629 will be administered intravenously at a dose and schedule as specified for the respective study part and cohort.
DRUGtocilizumab
Tocilizumab will be used as rescue medication only. Tocilizumab will be administered as required for the management of cytokine release syndrome (CRS).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable and/or metastatic HLA-G-positive solid tumors, for which standard therapy does not exist, or has proven to be ineffective or intolerable * Confirmed HLA-G tumor expression. * Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Life expectancy of at least 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate hematological, liver, renal and pulmonary function * Willingness to abide by protocol defined contraceptive requirements for the duration of the study.
Exclusion criteria
* History or clinical evidence of Central Nervous System (CNS) metastases unless protocol specified criteria are met * Leptomeningeal metastases * Rapid disease progression including lesions that are a threat to vital organs or non-irradiated lesions 2cm or larger at critical sites where tumor swelling may pose a risk to critical anatomical structures * Participants with another invasive malignancy in the last 2 years unless protocol specified criteria are met * Uncontrolled hypertension * Active interstitial lung disease (ILD), pneumonitis or a history of ILD/pneumonitis requiring treatment with steroids, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan * Participants with central cavitation or tumor(s) shown to be invading or abutting major blood vessels by imaging or the Investigator determines the tumor(s) is likely to invade major blood vessels and cause fatal bleeding * Participants with pulmonary military metastatic pattern or pulmonary lymphangitic carcinomatosis * History of pulmonary embolism within 3 months prior to study entry * Significant cardiovascular disease * Presence of active or uncontrolled infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to initiation of study treatment. * Known hepatitis B or C (actively replicating) based on protocol specified criteria * Known Human Immunodeficiency Virus (HIV) positivity * Presence of an indwelling line or drain * Active auto-immune disease that has required systemic therapy within the past 2 years unless protocol specified exceptions are met * Major surgery within 28 days prior to first study treatment * Last treatment with anti-cancer therapy or any investigational drug 28 days or less prior to the first study treatment * Last dose of immunostimulating or immunosuppressive therapy 28 days or less prior to the first study treatment * Regular dose of corticosteroids that exceeds prednisone 10 mg/day or equivalent within 28 days prior to first study treatment * Prior treatment with T cell engaging or adoptive cell therapy * Administration of a live, attenuated vaccine 28 days or less prior to first study treatment * Contraindication or known hypersensitivity to any of the components of RO7515629 or tocilizumab or dexamethasone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1, 2, 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 15 months |
| Part 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs) | From start of study treatment (cycle 0 day -7 or cycle 0 day -14) until two weeks after second or third RO7515629 infusion (cycle 1 day 1) for a total DLT window of up to 28 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1, 2, 3: Pharmacokinetic Analysis: Minimum Serum Concentration (Cmin) of RO7515629 | Up to 13 months | — |
| Parts 1, 2, 3: Pharmacokinetic Analysis: Clearance (CL) of RO7515629 | Up to 13 months | — |
| Part 1, 2, 3: Pharmacokinetic Analysis: Volume of Distribution at Steady State (Vss) of RO7515629 | Up to 13 months | — |
| Part 1, 2, 3: Pharmacokinetic Analysis: Area Under The Curve (AUC) of RO7515629 | Up to 13 months | — |
| Part 1, 2, 3: Number of Participants With RO7515629 Anti-drug Antibodies (ADAs) | Up to 13 months | — |
| Part 1, 2, 3: Pharmacokinetic Analysis: Maximum Serum Concentration (Cmax) of RO7515629 | Up to 13 months | — |
| Part 1, 2, 3: Disease Control Rate (DCR) | Up to approximately 18 months | — |
| Part 1, 2, 3: Duration of Response (DoR) | Up to approximately 18 months | — |
| Part 1, 2, 3: Progression Free Survival (PFS) | Up to approximately 18 months | — |
| Part 1, 2, 3: Overall survival (OS) | Up to approximately 18 months | Defined as the time from first dose of study treatment to time of death. |
| Part 1, 2, 3: Objective Response Rate (ORR) | Up to approximately 18 months | — |
| Part 1, 2, 3: Pharmacokinetic Analysis: Time of Maximum Serum Concentration (Tmax) of RO7515629 | Up to 13 months | — |
Countries
United States
Outcome results
None listed