This study has been transitioned to CTIS with ID 2022-501254-10-00 check the CTIS register for the current data. The purpose of this trial is to rollover participants who previously enrolled in MSD-sponsored pembrolizumab trials, including those who…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Respiratory tract neoplasms
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To estimate the overall survival (OS)
Secondary outcome
1. To estimate the Duration of Response (DOR) and Duration of Complete Response
(DOCR) per evaluation criteria used in the parent trial by investigator
assessment for participants who have received or are receiving First Course
Phase trial treatment with pembrolizumab or a pembrolizumab-based combination.
2. To evaluate the safety and tolerability of pembrolizumab or a
pembrolizumab-based combination in subjects who receive it as First or Second
Course Phase trial treatment.
Background summary
Pembrolizumab (also known as MK-3475, KEYTRUDA® and SCH900475) is a
potenthumanized immunoglobulin G4 (IgG4) monoclonal antibody with high
specificity of binding to the programmed cell death 1 (PD-1) receptor, thus
inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and
programmed cell death ligand 2 (PD-L2). Based on preclinical in vitro data,
pembrolizumab has high affinity and potent receptor blocking activity for PD-1.
Pembrolizumab has an acceptable preclinical safety profile and is in clinical
development as an intravenous (IV) immunotherapy for advanced malignancies.
Pembrolizumab is indicated for the treatment of patients across a number of
indications. Refer to the Investigator*s Brochure (IB)/approved labeling for
specific indications and detailed background information on pembrolizumab.
Study objective
This study has been transitioned to CTIS with ID 2022-501254-10-00 check the CTIS register for the current data.
The purpose of this trial is to rollover participants who previously enrolled
in MSD-sponsored pembrolizumab trials, including those who received
pembrolizumab, pembrolizumab-based combinations or control, into an extension
trial to collect long-term efficacy and safety data.
Study design
A Multicenter, Open label, Phase III Extension Trial to Study the Long-term
Safety and Efficacy in Participants with Advanced Tumors Who Are Currently on
Treatment or in Follow-up in a Pembrolizumab Trial.
Intervention
1. Pembrolizumab 200 mg every 3 weeks (Q3W) or 400 mg every 6 weeks (Q6W)
2. Pembrolizumab-based combinations (per parent trial)
3. Control arm (per parent trial)
Study burden and risks
All participants that rollover into this extension trial will be from MSD
pembrolizumab-based parent trials that have completed all regulatory
requirements and submissions, if any, including completion of the final
analysis database lock, or have fully addressed their primary endpoint(s).
Each participant will enroll in the trial from the time the subject provides
the informed consent through the final protocol-specified contact.
After consenting to enroll, each participant will roll-over to this extension
trial in one of the following three phases, depending on the study phase they
were in at the completion of the parent trial: 1) First Course Phase, 2)
Survival Follow-up Phase or 3) Second Course Phase. Participants who were in
the Follow-up Phase in the parent trial (posttreatment or Survival Follow-up
Phase) will enter the Survival Follow-up Phase of this trial.
Participants who were in the First Course Phase of trial treatment in their
parent trial will enter the First Course Phase of this trial and continue trial
treatment with pembrolizumab or a pembrolizumab-based combination until disease
progression is documented by the investigator per the parent trial evaluation
criteria, unacceptable adverse event(s) (AEs), intercurrent illness that
prevents further administration of trial treatment, investigator*s or
participant*s decision to withdraw the participant, noncompliance with trial
treatment or procedure
requirements, or administrative reasons requiring cessation of trial treatment.
In addition, for parent protocols where pembrolizumab dosing is without a
defined treatment period (ie. Keynote 001 [KN001], Keynote 002 [KN002]),
participants who had confirmed stable disease (SD) or better in their parent
trial may stop First Course Phase trial
treatment as long as they complete 35 doses of pembrolizumab (approximately 2
years). Participants who were allowed to continue trial treatment in their
parent trial with pembrolizumab or with a pembrolizumab-based combination
beyond disease progression at the investigator*s discretion (eg, KN001) will
enter First Course Phase and continue trial treatment with pembrolizumab or
with a pembrolizumab-based combination until unacceptable AEs, intercurrent
illness that prevents further administration of trial treatment, investigator*s
or participant*s decision to withdraw the participant, noncompliance with trial
treatment or procedure requirements, or administrative reasons requiring
cessation of trial treatment.
Participants who stopped First Course Phase trial treatment in their parent
trial or while on KN587, after receiving 35 doses or more of pembrolizumab or a
pembrolizumabbased combination for reasons other than disease progression or
intolerability, or participants who attained a CR and stopped trial treatment
may be eligible for 17 additional doses (approximately 1 year) of pembrolizumab
or a pembrolizumab-based combination (if allowed in the parent trial) upon
experiencing disease progression (Section 7.2.2). This will be considered the
Second Course Phase.
Participants who were in the Second Course Phase in their parent trial will
enter Second Course Phase of this trial and complete 17 doses of trial
treatment with pembrolizumab or a pembrolizumab-based combination (if allowed
in the parent trial), inclusive of the Second Course doses receive
in the parent trial. Under exceptional circumstances and upon Sponsor
consultation, participants may be allowed to continue to receive pembrolizumab
or a pembrolizumabbased combination beyond the 17 doses if the participant does
not meet any criteria for trial treatment discontinuation (Section.8.1). After
treatment discontinuation, participants will then be followed radiographically
by the site per standard of care (SOC) and for OS until death, withdrawal of
consent, start of a new antineoplastic therapy, or the end of the trial. This
will be considered the Survival Follow-up Phase. If a participant in Survival
Follow-up Phase has disease progression and is eligible for Second Course Phase
in this
trial, the participant will enter into Second Course Phase following a
determination of eligibility (Section 7.2.2). Once Second Course Phase trial
treatment is completed, participants will re-enter Survival Follow-up Phase.
Participants who were being treated in the First Course Phase in their parent
trial with a control (eg, chemotherapy) will enter Survival Follow-up Phase of
this trial and continue to be treated as per SOC. These participants will be
followed radiographically by the site per SOC and for OS until death,
withdrawal of consent, start of a new antineoplastic therapy, or the end of the
trial. After the end of trial treatment, each participant will be
followed for the occurrence of SAEs throughout 90 days and AEOSI and ECIs
throughout 30 days following the
discontinuation of trial treatment and for drug-related SAEs and spontaneously
reported pregnancy as described under
Section 9.3.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
1. Participants that are currently enrolled in MSD-sponsored
pembrolizumab trials and are receiving trial treatment or in a Follow-up
Phase at the time KN587 is open. Participants must be from MSD-sponsored
pembrolizumab parent trials established by the Sponsor as KN-587 transition
ready.
2. The participant (or legally acceptable representative if applicable)
provides informed consent for the trial and agrees to follow study
procedures.
Exclusion criteria
There are no exclusion criteria to participate in KN587., Participants are
excluded from entering Second Course trial treatment once they are enrolled on
KN587 if any of the following criteria applies:
1. Woman of Childbearing Potential who has a positive urine pregnancy test
within 72 hours prior to trial treatment allocation. If the urine test is
positive or cannot be confirmed as negative, a serum pregnancy test will be
required.
2. Has severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its
excipients (the list of excipients is provided in the IB).
3. Has received a live vaccine within 30 days prior to the first dose of Second
Course Phase trial treatment. Examples of live vaccines include, but are not
limited to, the following: measles, mumps, rubella, varicella/zoster (chicken
pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine.
Seasonal influenza vaccines for injection are generally killed virus vaccines
and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live
attenuated vaccines and are not allowed.
4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other
form of immunosuppressive therapy within 7 days prior to the Cycle 1 Day 1 of
Second Course Phase.
5. Has a known additional malignancy that is progressing or requires active
treatment. Exceptions include early stage cancers (carcinoma in situ or Stage
1) treated with curative intent, melanoma (non-ulcerated, thin primary), basal
cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ
cervical cancer, or in situ breast cancer that has undergone potentially
curative therapy.
6. Has known active central nervous system metastases and/or carcinomatous
meningitis.
7. Has an active autoimmune disease that has required systemic treatment in the
past 2 years (ie. use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed.
8. Has a history of (non-infectious) pneumonitis that required steroids or has
current pneumonitis.
9. NSCLC participants only: Has interstitial lung disease.
10. Has an active infection requiring systemic therapy.
11. Has a known history of human immunodeficiency virus infection.
12. Has a known history of or is positive for hepatitis B (hepatitis B surface
antigen reactive) or hepatitis C (hepatitis C virus RNA [qualitative] is
detected). Hepatitis C lab testing is allowed for eligibility purposes in
countries where hepatitis C virus RNA is not part of SOC.
13. Is pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the trial, starting with the Second Course
Phase eligibility Visit through 120 days after the last dose of trial treatment.
14. Has severe cardiovascular disease, ie. arrhythmias, requiring chronic
treatment, congestive heart failure (New York Heart Association Class III or
IV) or symptomatic ischemic heart disease.
15. Has hepatic decompensation (Child-Pugh score > 6 [class B and C]).
16. Has uncontrolled thyroid dysfunction.
17. Has uncontrolled diabetes mellitus.
18. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
participant's enrollment for the full duration of the trial, or is not in the
best interest of the participant to enroll, in the opinion of the treating
investigator.
19. Has known psychiatric or substance abuse disorders that would interfere
with cooperating with the requirements of the trial (specific testing is not
required).
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 |
|---|---|
| EU-CTR | CTIS2022-501254-10-00 |
| EudraCT | EUCTR2017-004417-42-NL |
| ClinicalTrials.gov | NCT03486873 |
| CCMO | NL65996.056.18 |