This study has been transitioned to CTIS with ID 2023-505067-36-00 check the CTIS register for the current data. Primary objective: To determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-1484…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Occurrence of Dose-Limiting Toxicity (DLT), Adverse Events (AE), and
discontinuation of study intervention due to an AE.
Secondary outcome
PK parameters of MK-1484, including area under the curve (AUC), minimum
concentration (Cmin), and maximum concentration (Cmax).
Background summary
The usefulness of Interleukin-2 (IL-2) as a therapeutic is hampered by its
short half-life and toxicity profile, which often leaves patients hospitalized
due to adverse events. As a result of these toxicities, it is rarely used.
Thus, the key features to improve on for an IL-2 based therapeutic are safety
profile and the half-life, which would enable more convenient administration.
MK-1484 is an agonistic analog of IL-2 with PEGylation for half-life extension.
In preclinical studies, MK-1484 showed antitumor activity in a mouse tumor
model and induced tumor growth inhibition. In these preclinical studies MK-1484
appeared to be well tolerated and showed limited elevation of eosinophils, a
known toxicity biomarker for aldesleukin (also a form of IL-2, used for
treatment of metastatic renal cell carcinoma). The favorable tolerability and
pharmacology profile in nonhuman primates validate the hypothesis and supports
selection of MK-1484 as a clinical candidate.
In this study, MK-1484 is further explored for the treatment of
advanced/metastatic solid tumors as monotherapy and as combination therapy with
pembrolizumab.
Study objective
This study has been transitioned to CTIS with ID 2023-505067-36-00 check the CTIS register for the current data.
Primary objective: To determine the safety and tolerability and to establish a
preliminary recommended Phase 2 dose (RP2D) of MK-1484 administered as
monotherapy and in combination with pembrolizumab infusion.
Secondary objective: To evaluate the PK of MK-1484 administered as monotherapy
and in combination with pembrolizumab.
Study design
MK1484-001 is a first-in-human, phase 1, multicenter, 2-arm, open-label, dose
escalation and dose confirmation study using an ATD, followed by mTPI design
strategy, to evaluate the safety and tolerability of MK-1484 as monotherapy and
in combination with pembrolizumab in adult participants with advanced or
metastatic solid tumors.
Intervention
This study has 2 intervention groups: participants in Arm 1 receive MK-1484
monotherapy and participants in Arm 2 receive MK-1484 in combination with
pembrolizumab. Each participant will receive assigned intervention for
approximately 2 years (35 cycles). MK-1484 is administered by subcutaneous
injection Q3W and pembrolizumab is administered by intravenous infusion Q3W.
If participants in Arm 1 experience disease progression, they may be eligible
for crossover to Arm 2 (criteria per protocol and upon sponsor approval).
Participants who crossover to combination treatment will be eligible to receive
a maximum of 35 cycles of combination treatment irrespective of the number of
cycles or dose of MK-1484 received in monotherapy.
Study burden and risks
By participating in this study, participants will be exposed to invasive
procedures (e.g. biopsy collection, blood collection and CT- or MRI-scans), are
asked to visit the hospital regularly, and receive experimental therapy with
unknown and potentially serious side effects. It is unsure if the participants
will directly benefit from the study intervention. There are however no
(approved) treatments left to confer clinical benefit for this patient
population.
MK-1484 has never been administered to humans. Similar drugs that work like
MK-1484 (e.g. next generation engineered IL-2 molecules NKTR-214, THOR-707 and
ALKS-4230) are known to have the following most common side effects: rash,
pruritus, fatigue, arthralgia, enlarged abdomen, nausea, malaise, chills,
fever, and changes in liver and kidney function (elevated transaminase and
blood urea nitrogen).
Pembrolizumab has been administered to a large number of oncology patients
(various indications) with a known safety profile. Pembrolizumab has been
approved for treatment of different types of cancer. Overall, pembrolizumab is
well tolerated with most common side effects being itchy skin, loose/watery
stools and coughing.
Participants are informed on the nature and extent of the burden and risks
associated with participation, as well as the potential benefit, by means of
the patient information sheet and the explanation from the investigator.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
# The participant has provided documented informed consent for this study.
# Male or female of at least 18 years at the time of signing the informed
consent form.
# Histologically- or cytologically-confirmed advanced/metastatic solid tumor by
pathology report and received, or intolerant to, all treatment known to confer
clinical benefit.
# Measurable disease by RECIST 1.1.
# Performance status of 0 or 1 on the ECOG Performance Scale (within 7 days
before the start of study intervention).
# Normal cardiac function based on TTE or MUGA.
# Presence of an evaluable archival or newly obtained tumor tissue sample for
biomarker analysis.
# Adequate organ function (within 7 days before the start of study
intervention).
# A male participant must agree to use contraception as detailed in the
protocol.
# A female participant is eligible to participate if not pregnant or
breastfeeding, agrees to follow the contraceptive guidance as detailed in the
protocol, or is not of child-bearing potential.
Exclusion criteria
# Chemotherapy, definitive radiation or biological cancer therapy within 4
weeks (2 weeks for palliative radiation) before the first dose of study
intervention.
# Not recovered to CTCAE Grade 1 or better from any AEs that were due to cancer
therapeutics administered more than 4 weeks earlier.
# Currently participating and receiving study intervention in a study of an
investigational agent, or participated and received study intervention in a
study of an investigational agent, or used an investigational device within 28
days of administration of MK-1484.
# Received any prior IL-2 based therapy.
# Allogeneic tissue/solid organ transplant in the last 5 years or evidence of
graft-versus-host disease.
# History of a second malignancy, unless potentially curative treatment has
been completed with no evidence of malignancy for 2 years.
# Clinically active CNS metastases and/or carcinomatous meningitis (exceptions
per protocol).
# History of severe hypersensitivity reaction to treatment with a monoclonal
antibody and/or components of the study intervention(s).
# Active infection requiring therapy.
# Active autoimmune disease that required systemic treatment in the past 2
years (details per protocol).
# History of interstitial lung disease, history of (noninfectious) pneumonitis
that required steroids, or current pneumonitis.
# Known HIV and/or hepatitis B or C infections, or known to be positive for
HBsAg/HBV DNA or hepatitis C Antibody or RNA.
# History or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant*s participation for the full duration of the study, make
administration of the study drugs hazardous, or make it difficult to monitor
adverse effects such that it is not in the best interest of the participant to
participate, in the opinion of the treating investigator.
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 | CTIS2023-505067-36-00 |
| EudraCT | EUCTR2021-005220-38-NL |
| CCMO | NL80286.056.22 |