RO7009789 and atezolizumab are experimental drugs that are being investigated by F. Hoffmann La Roche Ltd for the treatment of locally advanced and / or metastatic solid tumors.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Gevorderde en/of gemetastaseerde solide tumoren
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objectives of Part IA are:
*To evaluate the safety and tolerability of sequential administration (3 weeks
apart) of single-dose RO7009789 and atezolizumab
The primary objectives of Part IB are:
*To evaluate the safety and tolerability of a single dose administration of
RO7009789 concomitant with atezolizumab
*To determine the maximum tolerated dose (MTD) for the SC route of
administration (and potentially IV if this is tested) by observing the DLTs of
RO7009789 concomitant with
atezolizumab
*To determine a recommended Part II dose dose and route of administration of
RO7009789 ((either SC or IV in case this route of administration is tested in
part IB and selected) of RO7009789 for multiple concomitant treatments with
atezolizumab
The primary objectives of Part II are to study:
-safety, tolerability of multiple administrations of RO7009789 in combo with Ate
-optimal schedule of RO7009789 in combo with Ate
-Recommended Dose of RO7009789 for multiple concomitant treatment with Ate
-clinical activity of RO7009789 in combo with Ate in specific tumor types: head
and neck cancers (HNSCC), non-small cell lung carcinoma (NSCLC) and small and
large bowel carcinomas. Further indications may be selected.
Secondary outcome
The secondary objectives of Part IA are:
*To evaluate the pharmacokinetics of RO7009789 when administered as a single
agent
*To evaluate the pharmacokinetics of atezolizumab when given after RO7009789
administration
*To assess the biomarkers that might act as PD indicators of the
immune-modulatory effect and anti-tumor activity of RO7009789 (immune cell
numbers and proliferation status in peripheral blood as well as tumor immune
infiltration and PD-L1 expression levels in order to clarify the roles played
in anti-tumor activity)
*To explore the pharmacokinetic (PK) and PD (i.e., efficacy and safety
parameters) relationships following RO7009789 administration as a single agent
or after atezolizumab administration
*To characterize the immunogenic potential of RO7009789 and/or atezolizumab by
measuring anti-RO7009789 and anti- atezolizumab antibodies and assessing their
relationship with other outcome measures
The secondary objectives of Part IB are:
*To evaluate the pharmacokinetics of RO7009789 when administered concomitantly
with atezolizumab
*To evaluate the pharmacokinetics of atezolizumab when administered
concomitantly with RO7009789
*To preliminarily assess the clinical activity of RO7009789 when administered
concomitantly with atezolizumab as assessed by RECIST v1.1 and unidimensional
irRC
*To assess the biomarkers that might act as PD indicators of the
immune-modulatory effect and anti-tumor activity of RO7009789 concomitant with
atezolizumab (immune cells numbers and proliferation status in peripheral blood
as well as tumor immune infiltration and programmed death-ligand 1 [PD-L1]
expression levels in order to clarify th roles played in anti-tumotr activity)
*To explore the PK and PD (i.e., efficacy and safety parameters) relationships
following RO7009789 administration concomitant with atezolizumab
*To characterize the immunogenic potential of RO7009789 and/or atezolizumab by
measuring anti-RO7009789 and anti-atezolizumab antibodies and assessing their
relationship with other outcome measures
The secondary objectives of Part II are to study:
-PK multiple dose (MD) RO7009789 in combo with Ate, if appropriate
-PK MD Ate in combo with RO7009789
-PD biomarker of the immune-modulatory and anti-tumor activity of RO7009789 in
combo with Ate
-PK/PD rel.ships RO7009789 and Ate in a MD setting
-immunogenic potential RO7009789 and/or Ate by measuring ADA & assessing their
rel.ship with other outcome measures
-clinical activity RO7009789 in combo with Ate in selected tumor types
Background summary
This is a scientific study of RO7009789 and atezolizumab. These are both
monoclonal antibodies. A monoclonal antibody is a protein that is created when
the immune system detects the presence of harmful substances such as bacteria.
RO7009789 activates the cells of the body's immune system in order to kill the
tumor cells. Tumor cells respond by producing the protein, PD-L1 (programmed
death-1 ligand). This protein helps the tumor cells to survive. Atezolizumab
will PD-L1 block, which could have the effect that cancer cells will die. This
study aims to understand the effects of combined administration of RO7009789
and atezolizumab, at different doses and routes of administration, in patients
with locally advanced and / or metastatic solid tumors.
Study objective
RO7009789 and atezolizumab are experimental drugs that are being investigated
by F. Hoffmann La Roche Ltd for the treatment of locally advanced and / or
metastatic solid tumors.
Study design
Description of Study
This study is an open-label, multicenter, dose-escalation Phase Ib study
designed to assess the safety, pharmacokinetics, pharmacodynamics, and
therapeutic activity of RO7009789 administered in combination with
atezolizumab in patients with locally advanced and/or metastatic solid
tumors. There are 3 stages to this study, Part I (IA + IB), Part II, and Part
III (the design of Part III will depend on results of Part I and Part II).
Part IA is designed to verify the safety of SC administration of RO7009789 and
atezolizumab and to define the single-agent MTD of RO7009789 when administered
first in sequence with atezolizumab. A recommended dose of SC RO7009789 to be
used in combination with vaccines will also be determined.
Part IB is intended to verify the safety of a single concomitant administration
of RO7009789 (given SC and potentially IV) and atezolizumab and to define the
single-dose MTD of RO7009789 when administered concomitantly with atezolizumab.
In the event that the SC MTD is determined by injection site reactions, the IV
route of administration may be evaluated to establish if greater efficacy or
safety can be achieved. The starting IV dose will be at most 50% of the SC MTD
and not greater than 4 mg. At the MTD for both SC and IV, each cohort will be
expanded to 6-9 patients to generate PD, PK and safety data to establish the
most effective dose and route of administration for Part II.
Part II is designed to evaluate the safety, PK, PD and the clinical activity of
multiple administrations of the combination of RO7009789 and Atezolizumab in
patients with selected types of metastatic and/or locally advanced solid
tumours (including small bowel and CRC, NSCLC, head and neck squamous cell
carcinoma (HNSCC). Further indications may be selected). Additionally, the
dose, schedule and order of administration of RO7009789 will be refined.
Intervention
Patiënts eligible for participation in this study are treated with atezolizumab
& RO7009789 according to the study specific schedual as described in Appendix 1
(schedule of assessments) of the protocol.
Study burden and risks
Non-clinical and clinical safety data from atezolizumab and RO7009789
monotherapy studies show potential for immune-related events, and thus an
opportunity for increased immunity with a combination treatment of atezolizumab
and RO7009789. On the basis of these data, the possibility exists for the
combined agents for inducing or enhancing auto-immune disorders. Therefore
patients should be monitored for infusion-related reactions (IRR), cytokine
release, and immune-related side effects, and patients with pre-existing
autoimmune diseases were excluded from the study closely.
The most common adverse reactions in clinical studies already performed with
atezolizumab are: Abdominal pain, Anemia, Arthralgia (joint pain), Asthenia
(lack of energy), Chills, Constipation, Cough, Decreased appetite, Diarrhea,
Dyspnea (shortness of breath), Fatigue, Generalized pain and back pain,
Headache, Insomnia, Itching of the skin, Nausea, Peripheral edema (swelling of
the hands and feet), Pyrexia (fever), Rash, Vomiting (see protocol paragraph
1.1.1.2 for further information).
When given alone the most common side effects of RO7009789 when given
intravenously were infusion-related reactions (53% of patients).
Infusion-related reactions typically began within the first hour after
infusion. Symptoms include chills, fever, nausea, headache, high or low blood
pressure, fast heart rate and shortness of breath. These symptoms can be
managed by your physician, if necessary, with medications before administration
of RO7009789. Additional common side effects include tiredness (48% of
patients), nausea (34% of patients), headache (25% of patients) and chills (23%
of patients). Most of the patients who received RO7009789 subcutaneously
developed injection site reactions such as redness, itching, swelling,
induration, and tenderness 2 - 9 days later at the site of the injection. See
protocol paragraph 1.1.2.2 for further information.
The first patient who received the combination of RO7009789 (iv) and
atezolizumab experienced serious adverse events due to immune system activation
which resolved after corticosteroid treatment. Two further patients who were
treated with RO7009789 previously received atezolizumab safely.
The test procedures and treatments may entail risks and cause discomfort.
Mainly during the first administration (and up to 24 hours after) there is a
risk of an infusion-related reaction (IRR) or an allergic reaction. There is a
slight chance of pain or a bruise when blood is collected. Some people may
faint when blood is collected. During this study, with patient approval,
biopsies may be performed. The following risks are associated with a biopsy:
bruising, bleeding, infection and side-effects of the numbing medication
(anaesthetic) that may be given for the procedure. In rare cases, these risks
may be life-threatening and make hospitalization necessary. In order to reduce
the risks, the site of the biopsy will be numbed and sterile techniques will be
used.
Undergoing an MRI or PET / CT scan may entail additional discomfort,
specifically, a sense of claustrophobia (being *locked in*) or suffering from
the noise during the scan.
The disadvantages of participating in this study are: time investment from the
patient to undergo various procedures for this study, additional or prolonged
hospitalization(s), additional blood collection, additional examinations,
biopsies and possible side effects of RO7009789 & atezolizumab
Risk of drug interactions:
It is possible that treatment with atezolizumb and RO7009789 may affect the
operation of other medications.
The patient may experience one or more of these side-effects, or currently
unknown side effects, and they may be mild, moderate, severe, or (in very rare
cases) life-threatening or even fatal. If side-effects do occur, the study
physician must be notified immediately. He / she may prescribe medication to
combat any discomfort. Furthermore, in the event of a serious reaction, the
study physician may decide to suspend or permanently terminate treatment with
the study medication.
Beneluxlaan 2a
Woerden 3446GR
NL
Beneluxlaan 2a
Woerden 3446GR
NL
Listed location countries
Age
Inclusion criteria
*Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors that are not amenable to standard therapy
*Eastern Cooperative Oncology Group Performance Status of 0 or 1
*Life expectancy * 16 weeks
*Adequate hematologic and end organ function
*Measurable disease per RECIST v1.1
*Patient*s ability to comply with the collection of tumor biopsies. Tumors must be accessible for biopsy.
*Consent to undergo pretreatment and/or on-treatment biopsies for PD biomarker analysis
Exclusion criteria
*Any approved anti-cancer therapy that includes chemotherapy, hormonal therapy, or radiotherapy within 2 weeks prior to the first dose of study treatment
*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 (e.g., bone metastasis or osteoporosis) is allowed.
*Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate while on study.
*Uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent drainage procedures (one monthly or more frequently). 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 (e.g., hemophilia, von Willebrand*s disease, cancer-associated diffuse intravascular coagulation)
*Clinically meaningful proteinuria
*Requiring dialysis (peritoneal or hemodialysis)
*Known primary CNS malignancy or symptomatic or untreated CNS metastases
*History of autoimmune diseases
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2014-002835-32 |
| EudraCT | EUCTR2014-002835-32-NL |
| CCMO | NL50582.031.14 |