A Phase Ia/Ib Open Label, Dose-Escalation study of the Safety and Pharmacokinetics of RO7198457 as a Single Agent and in Combination with Atezolizumab in Patients with Locally Advanced or Metastatic Tumors.
- Conditions
- personal cancer vaccin study10027476
- Registration Number
- NL-OMON55424
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 28
• Age >=18
• Eastern Cooperative Oncology Group performance (ECOG) status of 0 or 1
• Life expectancy >= 12 weeks
• Adequate hematologic and end-organ function
• Measured or calculated creatinine clearance >= 50 mL/min
• Agrees to use protocol defined methods of contraception,
Cancer-Specific Inclusion Criteria
• Patients with histologic documentation of locally advanced, recurrent, or
metastatic incurable malignancy that has progressed after at least one
available standard therapy; or for whom standard therapy has proven to be
ineffective or intolerable, or is considered inappropriate; or for whom a
clinical trial of an investigational agent is a recognized standard of care
• Patients with measurable disease per Response Evaluation Criteria for Solid
Tumors v1.1, Additional Inclusion Criteria for Phase 1b Patients Who Backfill
Cleared Cohorts
• Backfill cohort enrollment may be limited to patients whose tumors have
programmed death-ligand 1 (PD-L1) and/or different levels of CD8 expression
• Backfill enrollment in Phase 1b may be managed such that approximately half
of the patients in each backfill cohort will not have been treated with prior
immune checkpoint inhibitors, except for those patients with tumor indications
where CIT is approved as therapy by local regulatory authorities.
Additional Inclusion Criteria for Patients in Each Phase 1b Indication-Specific
Exploration/Expansion Cohort
• Non-small cell lung cancer (NSCLC) Cohorts (CIT-Naïve): Patients with
histologically confirmed incurable, advanced NSCLC not previously treated with
anti-PD*L1/PD-1 and/or anti- cytotoxic T-lymphocyte-associated protein 4
(CTLA*4), for whom a clinical trial of an investigational agent in combination
with an anti-PD*L1 antibody is considered an acceptable treatment option
• NSCLC Cohort (CIT-Treated): Patients with histologically confirmed incurable,
advanced NSCLC previously treated with antiPD*L1/ PD-1 with or without anti
CTLA-4
• Triple Negative Breast Cancer (TNBC) Cohort (CIT-Naïve): Patients with
histologically confirmed incurable, advanced estrogen-receptor-negative,
progesterone receptor-negative, and human epidermal growth factor receptor 2
(HER-2)-negative adenocarcinoma of the breast (triplenegative) not previously
treated with anti-PD-L1/PD-1 and/or anti CTLA-4
• Colorectal cancer (CRC) Cohort (CIT-Naïve): Patients with histologically
confirmed incurable, advanced adenocarcinoma of the colon or rectum not
previously treated with anti-PD-L1/PD-1 and/or anti CTLA-4
• Head and Neck Squamous Cell Carcinoma (HNSCC) Cohort (CIT-Naïve): Patients
with histologically confirmed inoperable, locally advanced or metastatic,
recurrent, or persistent HNSCC not amenable to curative therapy not previously
treated with anti-PD-L1/PD-1 and/or anti CTLA-4
• Urothelial Carcinoma (UC) Cohort (CIT-Naïve): Patients with histologically
confirmed incurable, advanced transitional cell carcinoma of the urothelium,
including renal pelvis, ureters, urinary bladder, and urethra, not previously
treated with anti-PD*L1/PD-1 and/or anti-CTLA*4, for whom a clinical trial of
an investigational agent in combination with an anti-PD*L1 antibody is
considered an acceptable treatment option, if CIT (including anti-PD*L1/PD-1
agents) is approved as treatment for UC
• UC Cohort (CIT-Treated):
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study
entry.
• Pregnancy, breastfeeding, or intending to become pregnant during the study or
within 90 daysafter the last dose of RO7198457 or 5 months after the last dose
of atezolizumab, whichever occurs later
• Known clinically significant liver disease, including active viral,
alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or
current alcohol abuse
• Major surgical procedure within 28 days prior to Cycle (C) 1, Day (D) 1, or
anticipation of need for a major surgical procedure during the course of the
study
• Any other diseases, metabolic dysfunction, physical examination finding,
and/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 may render the patient at high risk
from treatment complications
• Previous splenectomy
• Known primary immunodeficiencies, either cellular or combined T- and B-cell
immunodeficiencies
• Any medical condition or abnormality in clinical laboratory tests that, in
the investigator's judgment, precludes the patient's safe participation in and
completion of the study,
Cancer-Specific Exclusion Criteria
• Any anti-cancer therapy, whether investigational or approved, including
chemotherapy, hormonal therapy, and/or radiotherapy, within 3 weeks prior to
initiation of study treatment
• Eligibility based on prior treatment with CIT and depends on the mechanistic
class of the drug and the cohort for which the patient is being considered
• Any history of an immune-mediated Grade 3 and 4 adverse event attributed to
prior CIT that resulted in permanent discontinuation of the prior
immunotherapeutic agent and/or occurred <=6 months prior to C1D1
• Adverse events from prior anti-cancer therapy that have not resolved to Grade
<= 1 except for alopecia, vitiligo, or endocrinopathy managed with replacement
therapy
• All immune-related adverse events related to prior CIT must have resolved
completely to baseline
• Primary central nervous system (CNS) malignancy, untreated CNS metastases, or
active CNS metastases, leptomeningeal disease
• Leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring
recurrent drainage procedures and hypercalcemia
• Malignancies other than disease under study within 5 years prior to C1D1,
with the exception of those with a negligible risk of metastasis or death
• Patient has spinal cord compression not definitively treated with surgery
and/or radiation or previously diagnosed and treated spinal cord compression
without evidence that disease has been clinically stable for >=2 weeks prior to
screening, Treatment-Specific Exclusion Criteria
• History of autoimmune disease
• Treatment with monoamine oxidase inhibitors (MAOIs) within 3 weeks
prior to Cycle 1, Day 1
• Treatment with systemic immunosuppressive medications within 2 weeks prior to
C1D1
• History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia,
or evidence of active pneumonitis on screening chest computed tomography scan
• Positive test for HIV infection
• Active hepatitis B
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. Incidence and nature of DLTs<br /><br>2. Incidence, nature, and severity of adverse events graded according to<br /><br>National Cancer Institute Common Terminology Criteria for Adverse Events (NCI<br /><br>CTCAE) v5.0<br /><br>3. Incidence, nature, and severity of immune-mediated adverse event graded<br /><br>according to NCI CTCAE v5.0<br /><br>4. Change from baseline in targeted vital signs<br /><br>5. Change from baseline in targeted clinical laboratory test results, including<br /><br>ECGs<br /><br>6. Number of cycles received and dose intensity.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Objective response (OR) defined as a complete response or partial response<br /><br>as per RECIST v1.1<br /><br>2. Duration of response (DoR) the time from the first occurrence of a<br /><br>documented objective response to the time of the first documented disease<br /><br>progression (DP)or death from any cause, whichever occurs first, per RECIST<br /><br>v1.1 as determined by the investigator<br /><br>3. OR and DoR as determined using immune-modified RECIST<br /><br>4. Progression free survival defined as the time from the first study treatment<br /><br>(D1) to the first occurrence of progression or death from any cause, whichever<br /><br>occurs first, per RECIST v1.1 as determined by the investigator<br /><br>5. Overall survival defined as the time from first study treatment to death<br /><br>from any cause<br /><br>6. Incidence of ADA to atezolizumab (Ph Ib) and the potential correlation with<br /><br>PK, pharmacodynamics, safety, and preliminary efficacy parameters.</p><br>