Primary objective:-To assess the efficacy of durvalumab plus olaparib combination therapy compared with durvalumab monotherapy in terms of PFS (Investigator-assessed)Secondary objectives:- To further assess the efficacy of durvalumab plus olaparib…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Endpoint Primary objective:
PFS: Time from date of randomization until the date of objective radiological
disease progression according to Investigator assessment using RECIST 1.1 or
death (by any cause in the absence of progression)
Statististical considerations can be found in the protocol summary
Secondary outcome
Endpoints secondary objectives
a) OS: Time from date of randomization until the date of death by any cause
ORR: Percentage of patients with an Investigator-assessed response of CR or PR
after Randomization
DoR: Time from the date of first documented response following randomization
until the first date of documented progression or death in the absence of
disease progression
b) PFS: Time from date of randomization until the date of objective
radiological disease progression according to Investigator assessment in HRRm
population using RECIST 1.1 or death (by any cause in the absence of
progression)
c) Concentration of durvalumab
d) Change from baseline and time to deterioration (for maintenance phase) in
EORTC QLQ-C30 and EORTC QLQ-LC13
e) Presence of ADAs for durvalumab
Endpoints safety objective
AEs, physical examinations, laboratory findings, and vital signs
Endpoints exploratory objectives
- Biomarkers (eg, TMB, alterations in HRR and other relevant gene variants,
protein expression detected by IHC, blood ctDNA, tumor and blood mRNA
expression, and PD-L1 expression) correlating with clinical response
- The EQ-5D-5L health state utility index will be used to derive health state
utility based on patient-reported data
- Change in specific treatment-related symptoms
- Proportion of patients assessing current symptom severity
- Health care resource use will be captured, including inpatient admissions,
intensive care unit admissions, and length of stay in hospital
Statististical considerations can be found in the protocol summary
Background summary
Rationale:
Current SoC therapies for metastatic non-small cell lung cancer (NSCLC) have
mixed outcomes with responses to systemic chemotherapy in the first-line
setting of approximately 20% to 40% and a median overall survival (OS) of
approximately 11 to 14 months (Breslow 1974, Carbone et al 2017, Paz-Ares et al
2013, Socinski et al 2018, Gandhi et al 2018). Treatments are associated with a
variety of significant side effects, including neutropenia, nausea, vomiting
and dehydration, and alopecia (Sandler et al 2006, Scagliotti et al 2008). The
KEYNOTE-024, KEYNOTE-042, KEYNOTE-189, and KEYNOTE-407 studies, along with the
IMpower131 and IMpower150 studies, have shown that immunotherapy alone or in
combination with chemotherapy can be effective first-line treatment for
patients with metastatic NSCLC (Gandhi et al 2018, Jotte et al 2018, Lopes et
al 2018, Paz-Ares et al 2018, Reck et al 2016, Socinski et al 2018). Results
from these studies have been encouraging and represent a substantive advance,
but further improvement is needed. All of the aforementioned studies yielded a
median progression-free survival (PFS) of <1 year. Furthermore, there are no
approved maintenance immunotherapy-based combination regimens for patients with
squamous histology. Increased DNA damage triggered through polyadenosine
5*diphosphoribose [poly (ADP ribose)] polymerase (PARP) inhibition has the
potential to not only provide antitumor activity but also modify tumor
immunogenicity and sensitize tumors to immune checkpoint inhibition, promoting
a more durable antitumor response. Therefore, in this Phase II study, the
combination of durvalumab plus olaparib will be investigated to determine if
this combination can prolong PFS in the maintenance setting in patients whose
Stage IV NSCLC has not progressed following SoC platinum-based chemotherapy
with durvalumab.
Study objective
Primary objective:
-To assess the efficacy of durvalumab plus olaparib combination therapy
compared with durvalumab monotherapy in terms of PFS (Investigator-assessed)
Secondary objectives:
- To further assess the efficacy of durvalumab plus olaparib combination
therapy compared with durvalumab monotherapy in terms of OS, ORR, and DoR
- To further assess the efficacy of durvalumab plus olaparib combination
therapy compared with durvalumab monotherapy in terms of PFS
(Investigator-assessed) in the HRRm population
- To assess the PK of durvalumab in combination with Olaparib
- To assess disease-related symptoms and HRQoL in patients treated with
durvalumab plus olaparib combination therapy compared with durvalumab
monotherapy
- To investigate the immunogenicity of durvalumab
Safety objective:
To assess the safety and tolerability profile of durvalumab plus olaparib
combination therapy compared with durvalumab monotherapy
Exploratory objectives:
- To assess blood and tissue samples at baseline (for initial therapy and
maintenance phases) and/or on-treatment for immune-related markers,
mRNA/protein signatures, and DNA mutations/signatures that are predictive of
clinical benefit to durvalumab plus olaparib combination therapy compared with
durvalumab monotherapy.
- To explore the impact of treatment and disease state on health utility using
the EQ-5D-5L
- To assess treatment-related side effects using PROCTCAE
- To assess the patient*s overall impression of the severity of their cancer
symptoms using PGIS
- To explore the impact of treatment and disease on health care resource use
Study design
Overall design:
This is a Phase II randomized, multi-center, double-blind, global study to
determine the efficacy and safety of durvalumab plus olaparib combination
therapy compared with durvalumab monotherapy as maintenance therapy in patients
whose disease has not progressed following SoC platinum-based chemotherapy with
durvalumab in first-line Stage IV NSCLC. There will be approximately 80 sites
in the study. During the initial therapy phase, approximately 350 to 400
patients will receive treatment with durvalumab, along with the Investigator*s
choice of platinum-based doublet therapy for squamous NSCLC (nanoparticle
albumin-bound [nab]-paclitaxel plus carboplatin or gemcitabine plus
carboplatin/cisplatin) and nonsquamous NSCLC (nab-paclitaxel plus carboplatin
or pemetrexed plus carboplatin/cisplatin) for 4 cycles.
It is estimated that approximately 350 to 400 patients will be enrolled in the
initial therapy phase in order for approximately 250 patients who have not
progressed (ie, maintained complete response [CR], partial response [PR], or
stable disease [SD] throughout the initial therapy phase according to
Investigator-assessed RECIST 1.1) to be randomized into the maintenance phase
of the study (patients completing the initial therapy phase who are not
randomized cannot continue durvalumab). Patients will be randomized 1:1 to
receive either durvalumab plus placebo or durvalumab plus olaparib maintenance
therapy. Randomization will be stratified by histologic subtype (squamous or
nonsquamous) and objective response (CR/PR or SD; obtained at the last visit
prior to randomization [Cycle 4 scan]) during the initial therapy phase.
Confirmation of eligibility criteria for randomization (eligibility scan and
other specific criteria; see Sections 5.1 and 5.2 for criteria that must be met
at randomization) will take place 14 to 28 days after Cycle 4 Day 1 of the
initial therapy phase. Laboratory assessments for eligibility should be taken
after the last dose of chemotherapy in the initial therapy phase. If determined
eligible, patients will be randomized within 5 weeks after Cycle 4 Day 1 of the
initial therapy phase; every effort should be made to minimize the time between
confirmation of eligibility, randomization, and starting maintenance treatment.
Patients will receive maintenance treatment until specific discontinuation
criteria are met, including clinical disease progression (as assessed by the
Investigator) or RECIST 1.1-defined radiological PD, unacceptable toxicity, and
withdrawal of consent. Note that crossover within the study will not be
permitted.
Intervention
Treatments and treatment duration:
Durvalumab (MEDI4736) and platinum-based chemotherapy (initial therapy phase)
During the initial therapy phase, all patients will receive durvalumab 1500 mg
via intravenous (IV) infusion q3w for 4 cycles, unless there is unacceptable
toxicity, withdrawal of consent, or another discontinuation criterion met. If a
patient*s WT falls to 30 kg or below, the patient should receive WT-based
dosing equivalent to 20 mg/kg of durvalumab q3w after consultation between
Investigator and Study Physician until the WT improves to >30 kg, at which
point the patient should start receiving the fixed dosing of durvalumab 1500 mg
q3w. If there is a dosing delay during the treatment schedule for durvalumab,
all future dosing days for durvalumab should be delayed to ensure that the
intervals between dosing study treatment are always at least 21 days. The
standard infusion time is 60 minutes. In the event that there are interruptions
during infusion, the total allowed time should not exceed 8 hours at room
temperature.
In addition to durvalumab, patients in the initial therapy phase will also
receive 1 of the following SoC regimens as part of their treatment regimen
(durvalumab will be infused first,followed by the SoC chemotherapy regimen):
-Nab-paclitaxel plus carboplatin (squamous and nonsquamous patients):
Nab-paclitaxel 100 mg/m2 via IV infusion on Days 1, 8, and 15 of each 3-week
cycle and carboplatin area under the concentration-time curve (AUC) 5 or 6 via
IV infusion on Day 1 of each 3-week cycle, for 4 cycles (Figure 2).
-Gemcitabine plus carboplatin (squamous patients only): Gemcitabine 1000 or
1250 mg/m2 via IV infusion on Days 1 and 8 of each 3-week cycle and carboplatin
AUC 5 or 6 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles (Figure
3).
-Gemcitabine plus cisplatin (squamous patients only): Gemcitabine 1000 or 1250
mg/m2 via IV infusion on Days 1 and 8 of each 3-week cycle and cisplatin 75
mg/m2 via IV infusion on Day 1 of each 3-week cycle, for 4 cycles (Figure 3)
-Pemetrexed plus carboplatin (nonsquamous patients only): Pemetrexed 500 mg/m2
and carboplatin AUC 5 or 6 via IV infusion on Day 1 of each 3-week cycle, for 4
cycles (Figure 4). Pemetrexed maintenance therapy will not be allowed following
the initial therapy phase.
- Pemetrexed plus cisplatin (nonsquamous patients only): Pemetrexed 500 mg/m2
and cisplatin 75 mg/m2 via IV infusion on Day 1 of each 3-week cycle, for 4
cycles (Figure 4). Pemetrexed maintenance therapy will not be allowed following
the initial therapy phase.
In the event that SoC is delayed during the initial therapy phase, durvalumab
administration must also be delayed.
In the event of unfavorable tolerability, patients can switch between cisplatin
and carboplatin therapy at any point during the study.
Durvalumab monotherapy and durvalumab plus olaparib combination therapy
(maintenance phase)
During the maintenance phase, all patients will receive durvalumab 1500 mg via
IV infusion every 4 weeks (q4w). Patients will also receive 300 mg oral
olaparib (durvalumab plus olaparib treatment arm) or its matching placebo
(durvalumab plus placebo treatment arm) BID continually until clinical disease
progression (as assessed by the Investigator) or RECIST 1.1-defined
radiological PD (Figure 5 and Figure 6), unless there is unacceptable toxicity,
withdrawal of consent, or another discontinuation criterion met.
Before commencing olaparib/placebo treatment, patients must first meet the
hematology/clinical chemistry requirements specified in Section 1.1 without
blood transfusions in the past 28 days.
If a patient*s WT falls to 30 kg or below, the patient should receive WT-based
dosing equivalent to 20 mg/kg of durvalumab q4w after consultation between
Investigator and Study Physician until the WT improves to >30 kg, at which
point the patient should start receiving the fixed dosing of durvalumab 1500 mg
q4w. If there is a dosing delay during the treatment schedule for durvalumab,
subsequent time between 2 consecutive doses of durvalumab cannot be less than
21 days; olaparib/placebo administration may continue as scheduled if
durvalumab is delayed. The standard infusion time for durvalumab is 60 minutes.
In the event that there are interruptions during infusion, the total allowed
time should not exceed 8 hours at room temperature.
See Section 7.1 for details about discontinuation of either durvalumab or
olaparib/placebo in the maintenance phase.
Duration of treatment
Unless specific treatment discontinuation criteria are met, treatment during
the initial therapy phase will continue for only 4 cycles of durvalumab plus
chemotherapy. There is no maximum treatment duration for the maintenance phase;
patients will receive maintenance treatment until specific discontinuation
criteria are met, including clinical disease progression (as assessed by the
Investigator) or RECIST 1.1-defined radiological PD, unacceptable toxicity, and
withdrawal of consent.
Progression during treatment
Patients with clinical disease progression (as assessed by the Investigator),
in the initial therapy or maintenance phase of the study, are not eligible for
treatment through progression. Patients who are clinically stable with RECIST
1.1-defined radiological PD at Cycle 2 of the initial therapy phase may
continue to receive study treatment at the discretion of the Investigator and
patient; however, if the patient continues to show a RECIST 1.1-defined
radiological PD at Cycle 4, the patient will not be eligible for the
maintenance phase of the study. Patients completing the initial therapy phase
who are not randomized cannot continue durvalumab.
During the maintenance phase, patients who are clinically stable at an initial
RECIST 1.1-defined radiological PD may continue to receive study treatment at
the discretion of the Investigator and patient. A follow-up scan is to be
collected after the initial RECIST 1.1-defined radiological PD, preferably at
the next (and no later than the next) scheduled imaging visit, and no less than
4 weeks after the prior assessment of PD; this follow-up scan is evaluated
using the Confirmation of Radiological Progression criteria outlined in
Appendix F. Patients with PD in the maintenance phase who continue to receive
investigational product (IP) at the discretion of the Investigator and patient
(following consultation with AstraZeneca) will have tumor assessments on their
regular imaging schedule for the duration of treatment. However, patients will
not be permitted to continue immunotherapy or olaparib/placebo if progression
occurs after confirmed response (CR or PR as defined by RECIST 1.1) in the
target lesions (TLs) to either the initial therapy (durvalumab plus
chemotherapy) or maintenance treatment (durvalumab or olaparib/placebo) of the
study regardless of the appearance of new lesions. Patients who have
discontinued durvalumab will not be permitted to be treated with
olaparib/placebo monotherapy after progression.
Follow-up of patients post discontinuation of study drug
Patients who have discontinued treatment in the maintenance phase for any
reason other than RECIST 1.1-defined radiological PD will be followed up with
tumor assessments until RECIST 1.1-defined radiological PD, plus one or more
additional follow-up scans if clinically feasible. Patients who discontinue
treatment due to RECIST 1.1-defined radiological PD will have one or more
additional follow-up scans, if clinically feasible. All patients will be
followed for survival. For patients who are not randomized into the maintenance
phase for any reason, follow-up tumor assessments will not be required.
Study burden and risks
- The risks associated with the study medications durvalumab (including iv
infusion) and olaparib.
- The risks associated with SOC chemotherapy
- The risks associated with the combination therapy of durvalumab with SOC
chemotherapy and the combination of durvalumab with olaparib
- The risk of possible interactions with other medications and grapefruit juice
- The risks linked to blood draws, MRI/CT scans and biopsies
These risks are included in the patient information sheet
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Listed location countries
Age
Inclusion criteria
Patients are eligible to be included in the study only if all of the following
inclusion criteria
and none of the exclusion criteria apply:
Informed consent
1 Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in
this
protocol.
2 Provision of signed and dated, written ICF prior to any mandatory study
specific
procedures, sampling, and analyses.
3 Provision of signed and dated written informed consent prior to collection of
sample for
genetic analysis.
The informed consent process is described in Appendix A 3 (protocol).
Patients must meet the following criteria at screening prior to receiving
treatment:
4 Female or male patients aged *18 years. For patients aged <20 years and
enrolled in
Japan, a written informed consent should be obtained from the patient and
his/her legally
acceptable representative.
5 Histologically or cytologically documented Stage IV NSCLC not amenable to
curative
surgery or radiation (according to version 8 of the IASLC Staging Manual in
Thoracic
Oncology; IASLC Staging Manual in Thoracic Oncology 2016).
6 Patients must have tumors that lack activating EGFR mutations (eg, exon 19
deletion or
exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation) and ALK
fusions. If a patient has squamous histology or is known to have a tumor with a
KRAS
mutation, then EGFR and ALK testing are not required.
7 World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG)
performance status (PS) of 0 or 1.
8 No prior chemotherapy or any other systemic therapy for Stage IV NSCLC.
Patients who
have received prior platinum-containing adjuvant, neoadjuvant, or definitive
chemoradiation are eligible, provided that progression has occurred >12 months
from end
of last therapy.
9 Life expectancy *12 weeks at screening.
10 Ability to swallow oral medications (capsules and tablets) without chewing,
breaking,
crushing, opening, or otherwise altering the product formulation. Patients
should not have
GI illnesses that would preclude the absorption of olaparib, which is an oral
agent.
11 Patients must also have adequate organ and marrow function without blood
transfusions
in the past 28 days, defined as follows:
- Hb *10 g/dL
- ANC *1.5 × 109/L
- Platelet count *100 × 109/L
- Serum bilirubin *1.5 × ULN; unless due to Gilbert*s syndrome, in which case
patients will be allowed in consultation with their physician and AstraZeneca
- ALT and AST *2.5 × ULN; for patients with hepatic metastases, ALT and AST *5 ×
ULN
- CrCl *51 mL/min calculated by the investigator or designee using the
Cockcroft-Gault equation (using actual body WT) or
measured by 24-hour urine collection
Males:
- CrCl <= WT (kg) × (140 - Age)
(mL/min) 72 × Serum creatinine (mg/dL)
Females:
- CrCl <= WT (kg) × (140 - Age) × 0.85
* (mL/min) 72 × Serum creatinine (mg/dL)
12 Patients must have at least 1 lesion, not previously irradiated, that can be
accurately
measured at baseline as *10 mm in the longest diameter (except lymph nodes that
must
have a short axis *15 mm) with computed tomography (CT) or magnetic resonance
imaging (MRI) and that is suitable for accurate repeated measurements as per
RECIST
1.1 guidelines.
13 All patients must provide a formalin-fixed, paraffin embedded (FFPE) tumor
sample for
tissue-based immunohistochemistry (IHC) staining and DNA sequencing to determine
PD-L1 expression, HRRm status, and other correlatives; either newly acquired or
archival
tumor samples (<3 years old) are acceptable. If available, a newly acquired
tumor biopsy,
collected as part of routine clinical practice, is preferred. If not available,
an archival
sample taken <3 years prior to screening is acceptable. If both an archival
sample and a
fresh tumor biopsy sample are available, both samples should be submitted for
analysis and must be submitted as different samples using different accesion
numbers. Slides from different blocks cannot be mixed and submitted with the
same kit.
14 Tumor lesions used for newly acquired biopsies should not be TLs, unless
there are no
other lesions suitable for biopsy. Samples with limited tumor content and fine
needle
aspirate specimens are not acceptable. Specimens from metastatic bone lesions
are
typically unacceptable unless there is a significant soft tissue component and
should not
be decalcified. For additional details on sample requirements, see Section
8.8.1 (protocol).
15 Body WT >30 kg.
Patients must meet the following criteria to be randomized to maintenance
treatment:
16 Patients must have documented radiographic evidence of a timepoint tumor
response of
CR, PR, or SD according to Investigator-assessed RECIST 1.1 guidelines
following the 4
cycles of platinum-based chemotherapy. An objective response does not have to be
confirmed in order for the patient to be randomized.
17 CrCl *51 mL/min calculated by the investigator or designee using the
Cockcroft-Gault equation (using actual body WT) or
measured by 24-hour urine collection.
18 Inclusion criterion 10.
Exclusion criteria
Patients must NOT meet the following criteria at screening prior to receiving
treatment:
1 Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an
interventional study.
2 Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology.
3 No radiation therapy is allowed, unless it is 1) definitive radiation that
had been
administered at least 12 months prior, 2) palliative radiation to brain, with
associated
criteria for stability or lack of symptoms, or 3) palliative radiation to
painful bony lesions
(this must comprise less than 30% of the bone marrow).
4 Prior exposure to any chemotherapy agents (with the exception of chemotherapy
or
chemoradiation for non-metastatic disease; see inclusion criterion 8 for full
details),
PARP therapy, or immune-mediated therapy, including, but not limited to, other
anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including
therapeutic
anticancer vaccines and other PARP inhibitors.
5 Any contraindications to platinum-based doublet chemotherapy.
6 Active or prior documented autoimmune or inflammatory disorders (including,
but not
limited to, inflammatory bowel disease [eg, colitis or Crohn*s disease],
diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome,
Wegener syndrome [granulomatosis with polyangiitis], Graves* disease, rheumatoid
arthritis, hypophysitis, uveitis, etc). The following are exceptions to this
criterion:
- Patients with vitiligo or alopecia
- Any chronic skin condition that does not require systemic therapy
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement
- Patients without active disease in the last 5 years may be included but only
after
consultation with AstraZeneca.
- Patients with celiac disease controlled by diet alone may be included but
only after
consultation with AstraZeneca.
7 History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease *5
years
before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of
disease
- Adequately treated carcinoma in situ without evidence of disease
8 Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (eg,
hormone
replacement therapy) is acceptable.
9 Current or prior use of immunosuppressive medication within 14 days before
the first
dose of IP. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg,
intra-articular
injection)
- Systemic corticosteroids (that are not excluded according to exclusion
criterion 10) at
physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan
premedication)
10 Concomitant use of known strong cytochrome P450 (CYP) 3A (CYP3A) inhibitors
(eg,
itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with
ritonavir or
cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, and telaprevir) or
moderate
CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, and
verapamil). The required washout period prior to starting study treatment is 2
weeks.
Concomitant use of known strong (eg, phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St. John*s
Wort) or
moderate CYP3A inducers (eg, bosentan, efavirenz, dexamethasone, and
modafinil). The
required washout period prior to starting study treatment is 5 weeks for
enzalutamide or
phenobarbital and 3 weeks for other agents.
11 Major surgical procedure (as defined by the Investigator) within 28 days
prior to the first
dose of IP. Note: Local surgery of isolated lesions for palliative intent is
acceptable.
12 Resting ECG indicating uncontrolled, potentially reversible cardiac
conditions, as judged
by the Investigator (eg, unstable ischemia, uncontrolled symptomatic
arrhythmia, QT
interval corrected for heart rate using Fridericia*s formula [QTcF] value *470
ms
calculated from 3 ECGs [within 15 minutes at 5 minutes apart], electrolyte
disturbances,
etc), or patients with congenital long QT-interval syndrome or congestive heart
failure.
13 Has untreated central nervous system (CNS) metastases and/or carcinomatous
meningitis
identified either on the baseline brain imaging (please see Appendix F [RECIST]
for
details on the imaging modality) obtained during the screening period or
identified prior
to signing the ICF. Patients whose brain metastases have been treated may
participate
provided they show radiographic stability (defined as 2 brain images, both of
which are
obtained after treatment to the brain metastases. These imaging scans should
both be
obtained at least 4 weeks apart and show no evidence of intracranial
progression). In
addition, any neurologic symptoms that developed either as a result of the brain
metastases or their treatment must have resolved or be stable either, without
the use of
steroids, or are stable on a steroid dose of *10 mg/day of prednisone or its
equivalent and
anti-convulsants for at least 14 days prior to the start of treatment. Brain
metastases will
not be recorded as RECIST TLs at baseline.
14 Uncontrolled intercurrent illness, including, but not limited to, ongoing or
active
infection, symptomatic congestive heart failure, uncontrolled hypertension,
unstable
angina pectoris, cardiac arrhythmia, ILD, or psychiatric illness, or social
situations that
would limit compliance with study requirements, substantially increase the risk
of
incurring AEs from IP, or compromise the ability of the patient to give written
informed
consent.
15 History of allogenic organ transplantation including umbilical cord blood
transplantation.
16 Patients with MDS/acute myeloid leukaemia or with features suggestive of
MDS/AML
17 History of leptomeningeal carcinomatosis.
18 History of active primary immunodeficiency.
19 Active infection including tuberculosis (clinical evaluation that includes
clinical
history, physical examination and radiographic findings, and tuberculosis
testing in line
with local practice), hepatitis B (known positive hepatitis B virus [HBV]
surface antigen
[HBsAg] result), hepatitis C, or human immunodeficiency virus (HIV; positive HIV
1/2 antibodies). Patients with a past or resolved HBV infection (defined as the
presence of
hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive
for
hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction
is
negative for HCV ribonucleic acid (RNA).
20 Any unresolved toxicity NCI Common Terminology Criteria for Adverse Event
(CTCAE) Grade *2 from previous anticancer therapy with the exception of
alopecia,
vitiligo, and the laboratory values defined in the inclusion criteria:
- Patients with Grade *2 neuropathy will be evaluated on a case-by-case basis
after
consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated
by
treatment with durvalumab or olaparib may be included only after consultation
with
the Study Physician.
21 Known allergy or hypersensitivity to any of the study drugs or any of the
study drug
excipients.
22 Receipt of live attenuated vaccine within 30 days prior to the first dose of
IP. Note:
Patients, if enrolled, should not receive live vaccine while receiving IP and
up to 30 days
after the last dose of IP.
23 Participation in another clinical study with an IP administered in the last
12 months.
24 Previous IP assignment in the present study.
25 Prior randomization or treatment in a previous durvalumab (and/or olaparib)
clinical
study regardless of treatment arm assignment.
26 Female patients who are pregnant or breastfeeding or male or female patients
of
reproductive potential who are not willing to employ effective birth control
from
screening to 90 days after the last dose of durvalumab or 30 days after the
last dose of
olaparib/placebo, whichever is later.
27 Judgment by the Investigator that the patient should not participate in the
study if the
patient is unlikely to comply with study procedures, restrictions, and
requirements.
28 Genetics research study (optional):
Exclusion criteria for participation in the optional (DNA) genetics research
component of
the study include:
- Previous allogeneic bone marrow transplant
- Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample
collection
Patients must NOT meet the following criterion to be randomized to maintenance
treatment:
29 Inability to complete 4 cycles of platinum-based chemotherapy for any reason
or
discontinuation of durvalumab during initial therapy. Dose interruptions or
delays are not
exclusionary.
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 |
|---|---|
| EudraCT | EUCTR2018-003460-30-NL |
| ClinicalTrials.gov | NCT03775486 |
| CCMO | NL67473.028.18 |