The aim of this prospective, multicentre randomized phase II study is to evaluate the safety and efficacy of the combination of capmatinib and spartalizumab in subjects with EGFR weight (for exon 19 deletions and exon 21 L858R substitution mutations…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In the run-in part safety and tolerability data will be assessed when all
patients in this phase have at least 24 weeks of follow-up as well as
preliminary efficacy.
Secondary outcome
In the randomized part, the primary analysis will be performed when
approximately 60 overall survival events have been observed. Overall Survival
(OS) is defined as the time from the date of randomization/start of treatment
to date of death due to any cause. A cut-off date will be established for
analysis of OS. All deaths occurring on or before the cut-off date in the Full
Analysis Set (FAS) will be used in the OS analysis. If a patient is not known
to have died at the time of analysis cut-off, OS will be censored at the date
of last contact. The analysis of OS will be based on full analysis set which
includes who received at least one dose of any component of study treatment and
all randomized subjects. The estimated hazard ratio (HR) between capmatinib and
spartalizumab combination and docetaxel and exact 80% confidence interval will
be assessed. The expected median OS for docetaxel as second-line chemotherapy
is ~8 months (Herbst et al 2016, Rittmeyer et al 2017). A 33.3% reduction in
hazard rate for overall survival in capmatinib plus spartalizumab arm compared
to docetaxel arm will correspond to an increase in median OS by 4 months under
the exponential assumption. Considering a 2:1 randomization, with approximately
60 OS events, the probability
of observing clinically relevant activity is 66% when the true HR is 0.60 and
the probability of observing clinically relevant activity is 24% when the true
HR is 0.80. The secondary efficacy endpoints, objective response rate (ORR),
disease control rate (DCR), progression free survival (PFS), time to response
(TTR), duration of response (DOR) and disease control rate (DCR) based on the
investigator assessed as per RECIST 1.1 will be analyzed.ORR and DCR will be
summarized with accompanying 95% confidence interval (CI). PFS, TTR, DOR and
the Kaplan-Meier curves, medians and 95% confidence intervals of the medians
will be presented.
Background summary
Capmatinib is in a tablet that is taken by mouth. It is a so-called targeted
medicine. This means that it is aimed at a certain process that does not work
well in the cancer cells in your body. It is possible that your lung cancer is
caused thereby.
Spartalizumab is a so-called monoclonal antibody. That is a protein that
attaches itself to a certain body protein, called PD-1. As a result,
spartalizumab can increase the efficacy of certain cells of the body's immune
system. This allows the immune system of the body to better fight the tumor
cells. This can then delay tumor growth.
The combination of capmatinib and spartalizumab is currently being tested in
the form of a liver cancer. There are also reasons to believe that this
combination has a beneficial effect in patients with NSCLC.
Capmatinib and spartalizumab are not yet authorized ("registered") by the Dutch
government as a medicine. Doctors are therefore not allowed to prescribe the
drugs to patients with NSCLC or other diseases. Registration with patients is
required for registration.
As mentioned, docetaxel is the standard treatment for the type of lung cancer
you have. Docetaxel is a form of chemotherapy and is a cell-killing substance.
In the current study we want to compare the efficacy and safety of the
combination of capmatinib and spartalizumab with the effects of docetaxel.
Docetaxel has been registered for the treatment of advanced or metastatic
NSCLC. Administration of docetaxel is done in the way it is registered.
Capmatinib and spartalizumab are made by Novartis and docetaxel by another
company.
The research consists of two parts. You participate in one of both parts:
Part 1: Part 1 is performed to assess the safe and tolerated doses of
capmatinib and spartalizumab. Approximately 15 test subjects participate in
part 1.
Part 2: In part 2 the efficacy, safety and tolerability of the combination of
capmatinib and spartalizumab are compared with those of docetaxel.
Approximately 90 test subjects participate in part 2.
Study objective
The aim of this prospective, multicentre randomized phase II study is to
evaluate the safety and efficacy of the combination of capmatinib and
spartalizumab in subjects with EGFR weight (for exon 19 deletions and exon 21
L858R substitution mutations), ALK-negative rearrangement, advanced /
metastatic (stage IIIB (not susceptible to definitive chemo-radiotherapy) or
IV) NSCLC, regardless
MET and PD-L1 status The study will enroll test subjects with advanced /
metastatic NSCLC who are EGFR-wt, ALK-negative, after failure of previous
platinum doublet and calibration point inhibitor administered for the treatment
of the advanced stage disease. Topics must be
docetaxel naive. A run-in part is performed to determine the safety and
tolerability and preliminary efficacy of the combination of capmatinib and
spartalizumab. Randomized part will be performed to assess the overall survival
(OS) of the combination of capmatinib and spartalizumab compared with docetaxel
Study design
This is a two-part prospectively designed, multicenter, open-label, randomized
phase II study to evaluate the safety and the efficacy of capmatinib in
combination with spartalizumab in adult subjects with EGFR wild type and ALK
rearrangement negative advanced stage IIIB or IV NSCLC after failure of
platinum doublet chemotherapy and checkpoint inhibitor treatment. Part 1:
run-in phase: will confirm the safety and tolerability and assess the efficacy
of the combination of capmatinib and spartalizumab. Part 2: randomized phase:
will evaluate the efficacy and safety of the combination
of capmatinib and spartalizumab compared to docetaxel
Intervention
Treatment with capmatinib and spartalizumab combination or docetaxel.
Study burden and risks
Subjects in this study have advanced non-small cell lung cancer and have
progressed after one or two lines of prior approved chemotherapy, radiotherapy
and/or immunotherapy. Given the clinical and molecular characteristics of their
disease they have limited therapeutic options and
the established standard, single agent chemotherapy regimens approved for this
setting are of limited benefit. Synergistic antitumor effect has been shown
preclinically with capmatinib in combination with checkpoint inhibitors in
non-MET driven tumor models. The safety profile of capmatinib and spartalizumab
as monotherapies is well characterized (see Section 1.1.1 and Section 1.1.2).
This new combination has been proven to be safe at the dose of 400 mg BID
capmatinib and spartalizumab 300 mg Q3W in HCC subjects treated in study
[CINC280X2108] (see
Section 1.1.3.2). The 24 weeks follow-up of this run-in phase is intended not
only to allow a thorough assessment of the safety profile of this new schedule
but also to assess the preliminary efficacy of this combination before
enrolling more subjects into the randomized part.
Appropriate eligibility criteria and stopping rules are included in this
protocol. Recommended guidelines for prophylactic or supportive treatment for
expected toxicities, including the management of study-drug induced AEs, (e.g.
infusion reaction, pneumonitis) are provided in Section 6.5. The risk to
subjects in this trial may be minimized by compliance with the eligibility
criteria and study procedures, as well as by close clinical monitoring.
Oncology Clinical Trial Protocol (Version No. 00) Protocol No. CINC280D2201 As
with any clinical study, there may be unforeseen risks with the combination
studied, which could be serious. The specific risks for each compound are
discussed below.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
* Histologically confirmed locally advanced/metastatic (stage IIIB/IV) per
AJCC/IASLC v.8) NCSCL
* EGFR wild-type, ALK rearrangement negative, NSCLC
* Subject has demonstrated progression following one prior platinum doublet and
one prior PD-(L)1 checkpoint inhibitor (either alone or in combination, the most
recent treatment regimen must have contained a PD-(L)1 checkpoint inhibitor)
* Subjects must be candidates for single agent docetaxel
* Subjects must have at least one lesion evaluable by RECIST 1.1
Exclusion criteria
* Prior treatment with a MET inhibitor or HGF (Hepatocyte growth factor)
targeting
therapy
* Any untreated central nervous system (CNS) lesion
* Use of any live vaccines against infectious diseases within 12 weeks of
initiation
of study treatment
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 | EUCTR2018-001420-19-NL |
| ClinicalTrials.gov | NCT03647488 |
| CCMO | NL67932.091.18 |