This study has been transitioned to CTIS with ID 2023-506987-15-00 check the CTIS register for the current data. 1) Objective: To evaluate the safety and tolerability of the pembrolizumab combination therapy.2) Objective: To estimate PSA response…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective(s) & Hypothesis(es) 1) Objective: To evaluate the safety
and tolerability of the pembrolizumab combination therapy. 2) Objective: To
estimate PSA response rate of the pembrolizumab combination therapy. PSA
response is defined as a reduction in the PSA level of 50% or more from
baseline measured twice at least 3 weeks apart. 3) Objective: To estimate the
objective response rate (ORR) based on RECIST 1.1 assessed by BICR.
Secondary outcome
1) Time to PSA progression
2) Overall response rate (ORR)
3) Radiographic progression-free survival (rPFS)
4) Overall Survival (OS)
5) the duration of response (DOR) based on RECIST 1.1
6) disease control rate (DCR) based on RECIST 1.1
7) For cohort A only:
- response according to RECIST 1.1 by BICR
- PSA response rate
- conversion in the circulating tumor-cell (CTC) count.
8) Safety and toleability (Adverse events (AEs)
Background summary
Prostate cancer represents one of the most commonly diagnosed cancer
malignancies and the second leading cause of cancer-related deaths in men
worldwide. There remains an unmet medical need for patients with mCRPC with
disease progression following treatment with a new hormonal agent and/or
docetaxel-based chemotherapy.
Pembrolizumab is a potent humanized IgG4 monoclonal antibody (mAb) with high
specificity of binding to the programmed cell death 1 (PD-1) receptor, thus
inhibiting its interaction with ligand PD-L1 and ligand 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. Keytruda® (pembrolizumab) is indicated for the treatment
of patients across a number of indications.
The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to
suppress immune control. The normal function of PD-1, expressed on the cell
surface of activated T- cells under healthy conditions, is to down-modulate
unwanted or excessive immune responses, including autoimmune reactions. As a
consequence, the PD-1/PD-L1 pathway is an attractive target for therapeutic
intervention in mCRPC.
Study objective
This study has been transitioned to CTIS with ID 2023-506987-15-00 check the CTIS register for the current data.
1) Objective: To evaluate the safety and tolerability of the pembrolizumab
combination therapy.
2) Objective: To estimate PSA response rate of the pembrolizumab combination
therapy. PSA response is defined as a reduction in the PSA level of 50% or more
from baseline measured twice at least 3 weeks apart.
3) Objective: To estimate the objective response rate (ORR) based on RECIST 1.1
assessed by BICR.
Study design
This is a nonrandomized (with the exception of Cohort I and J which are
randomized 1:1), multicenter, multicohort, open-label, Phase Ib/II trial of
pembrolizumab (MK-3475) combination therapy in subjects with metastatic
castration-resistant prostate cancer
(mCRPC).
Approximately 1200 participants will be assigned to one of the cohorts.
Screening procedures are to be completed within 42 days prior to treatment
allocation/randomization
Subjects will be assigned to one of the following cohorts based on prior
treatment for mCRPC and other eligibility criteria for each cohort. The
investigator*s choice of standard of care will also be used to allocate
subjects due to some overlap in entrance criteria. Cohorts A, B, C, D, E, G,
and J will enroll subjects with adenocarcinoma (AC); Cohorts F, H, and I will
enroll subjects with treatment emergent neuroendocrine (t-NE) cancer.
Intervention
Cohort A (AC) (closed):
Pembrolizumab 200 mg intravenous (IV) every 3 weeks (Q3W)
+ olaparib 400 mg (capsules)/300 mg (tablets) by mouth (PO)
twice a day (bid)
Cohort B (AC) (closed):
Pembrolizumab 200 mg IV q3w + docetaxel 75 mg/m2 IV Q3W
+ prednisone 5 mg PO bid
Cohort C (AC) (closed):
Pembrolizumab 200 mg IV q3w + enzalutamide 160 mg PO
every day (QD)
Cohort D (AC) (closed):
Pembrolizumab 200 mg IV Q3W + abiraterone acetate 1000 mg
PO qd + prednisone 5 mg PO bid
Cohort E (AC):
Pembrolizumab 200 mg IV Q3W + lenvatinib 20 mg PO QD
Cohort F (t-NE):
Pembrolizumab 200 mg IV q3w + lenvatinib 20 mg PO QD
Cohort G (AC):
Pembrolizumab 200 mg IV Q3W + MK-7684 (vibostolimab)
200 mg IV Q3W coformulation (MK-7684A)
Cohort H (t-NE):
Pembrolizumab 200 mg IV Q3W + MK-7684 (vibostolimab)
200 mg IV Q3W coformulation (MK-7684A)
Cohort I (t-NE):
Subjects will be randomly assigned on a 1:1 ratio to receive chemotherapy with
(Arm 1) or without pembrolizumab (Arm 2); both arms are t-NE.
Arm 1: Pembrolizumab 200 mg IV Q3W + carboplatin titrated to an AUC of 5 IV Q3W
on Day 1 + etoposide 100 mg/m2 IV Q3W on Days 1, 2, and 3.
Arm 2: Carboplatin titrated to an AUC of 5 IV Q3W on Day 1 + etoposide 100
mg/m2 IV Q3W on Days 1, 2, and 3.
Cohort J (AC):
Approximately 20 participants will be enrolled in the initial cohort to receive
belzutifan monotherapy 120 mg
QD (Arm J1). If an efficacy signal is detected in the monotherapy arm based on
a totality of evidence, Cohort
J may be expanded where subsequent 180 participants will be randomized 1:1 to
receive either belzutifan 120 mg QD
(Arm J1) or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W (Arm J2), about
90 per arm in the expansion
cohort. Arm J1 will explore the safety and efficacy of belzutifan monotherapy.
Arm J2 will explore the safety
and efficacy of the combination of belzutifan and pembrolizumab. Exploratory
analyses of between-group
comparisons for Cohort J without formal hypothesis testing may be conducted in
this estimation study.
Arm J1: Belzutifan 120 mg QD
Arm J2: Pembrolizumab 200 mg IV Q3W + belzutifan 120 mg QD
Note: (Amendment 08), Cohorts A, B, C, and D are fully enrolled and closed to
enrollment
Study burden and risks
For this study, patients will be subjected to invasive procedures such as blood
collection, Biopsy, CT-MRI or bone scans, physical exams, possibly
confrontational questionnaires, and patients will be asked to visit the
hospital regularly. Patients will be administered with different combination
threapies, during three-week cycles up to a maximum of 35 treatments.
It cannot be guaranteed that participants in clinical studies will directly
benefit from study intervention during participation, as clinical studies are
designed to provide information about the safety and effectiveness of an
investigational medicine. Pembrolizumab has been administered in a large number
of cancer participants with a well characterized safety profile and has
received regulatory approval for multiple malignancies. Overall, pembrolizumab
is well tolerated at doses up to 10 mg/kg every 2 weeks (Q2W). Pembrolizumab
has also demonstrated anticancer clinical activity and efficacy in a broad
range of cancer indications.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
The below-mentioned inclusion criteria are the most important ones. A complete
list of cohort specific inclusion criteria can be found in the protocol. - Be
willing and able to provide documentad written informed consent/assent for the
trial - Be >= 18 years of age on day of signing informed consent - Have
histologically- or cytologically-confirmed adenocarcinoma of the prostate
without small cell histology (cohorts A-E, G, J) - Have t-NE prostate cancer
defined by >=1% neuroendocrine cells in a recent biopsy specimen from a
metastasis - Have provided tumor tissue from a site not previously irradiated -
Have prostate cancer progression within 6 months prior to screening - Have
progression if the subject received anti-androgen therapy prior to enrollment -
Have ongoing androgen deprivation with serum testosterone <50 ng/dl -
Subjects receiving bone resorptive therapy must have been on stable doses for
>=4 weeks prior to first dose of trial treatment - Agree to use an adequate
method of contraception, if the subject is of reproductive potential, starting
with the first dose of study therapy through 120 days after the last dose of
study therapy - Demonstrate adequate organ function
Exclusion criteria
The below-mentioned exclusion criteria are the most important ones. A complete
list of cohort specific exclusion criteria can be found in the protocol.
- Has had prior anticancer mAb within 4 weeks prior to first dose of trial
treatment of who has not recovered form AEs due to mAbs administered more than
4 weeks prior to first dose of trial treatment
- Is currently participating in and receiving study therapy or has participated
in a study of an investigational device within 4 weeks of randomization
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days of randomization
- If a subject has undergone major surgery, they must have recovered adequately
from the toxicities/complications prior to starting therapy
- Has had a prior radium treatment or treatment with other therapeutic
radiopharmaceuticals for prostate cancer
- Has a known additional malignancy that has had progression or has required
active treatment in the last 3 years
- Has an active autoimmune disease that has requires systemic treatment in past
2 years
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required
steroids or current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy
- has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the
best interest of the subject to participate, in the opinion of the investigator
- has known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the trial
- Has previously participated in any other pembrolizumab trials, or received
prior therapy with an anti-PD-1, anti-PD-L1 and anti-PD-L2
- Has known history of HIV
- Has known active hepatitis B, or C virus
- Has received a live vaccine within 30 days of the first dose of trial
treatment
- Has used herbal products that may have hormonal anti-prostate cancer activity
and/or are known to decrease PSA levels within 4 weeks prior to randomization
- Has known active central nervous system metastases and/or carcinomatous
meningitis
- Has had prior chemotherapy, targeted small molecule therapy, abiraterone
acetate treatment, enzalutamide treatment, or radiation therapy within 2 weeks
prior to first dose of trial treatment or who has not recovered from AEs due to
previously administered agent
- Has a "superscan" bone scan
- Has had prior solid, organ or bone marrow transplant
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 | CTIS2023-506987-15-00 |
| EudraCT | EUCTR2016-002312-41-NL |
| ClinicalTrials.gov | NCT02861573 |
| CCMO | NL75767.028.21 |