A Phase 1, Open-label, Multicenter Study of the Safety, Pharmacokinetics, and Pharmacodynamics of MK-4464 as Monotherapy and in Combination with Pembrolizumab in Participants with Advanced / Metastatic Solid Tumors
- Conditions
- advanced or metastatic solid tumorssolid neoplasm10027656
- Registration Number
- NL-OMON53771
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 30
A participant will be eligible for inclusion in the study if the participant
meets the following
criteria:
1. Have a histologically or cytologically confirmed advanced/metastatic solid
tumor by pathology report and have received, or been intolerant to, all
treatment known to confer clinical benefit. Only solid tumors of the following
types may be included:
• CRC
• Gastric carcinoma
• Esophageal carcinoma
• Pancreatic cancer
• NSCLC
2. Have measurable disease by RECIST 1.1 as assessed by the local site
investigator/radiology. Target lesions situated in a previously irradiated area
are considered measurable if progression has been shown in such lesions.
3. Must submit a baseline tumor sample for analysis (either a recent or
archival tumor sample). Details pertaining to tumor tissue submission can be
found in the Laboratory Manual.
4. Arm A (mTPI part): Have 1 or more discrete malignant lesions that are
amenable to biopsy.
5. Have a performance status of 0 or 1 on the ECOG Performance Scale.
6. Have adequate organ function as defined in the protocol. Specimens must be
collected within 7 days before the start of study intervention.
7. Is male or female, >=18 years of age at the time of providing informed
consent.
8. No contraception measures are required for male participants.
9. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
• Not a WOCBP
• A WOCBP and:
- Uses a contraceptive method that is highly effective (with a failure rate of
<1% per year), or be abstinent from heterosexual intercourse as their preferred
and usual lifestyle (abstinent on a long-term and persistent basis) during the
intervention period and for at least 120 days after the last dose of study
intervention. The investigator should evaluate the potential for contraceptive
method
failure (ie, noncompliance, recently initiated) in relationship to the first
dose of study intervention. Contraceptive use by women should be consistent
with local regulations regarding the methods of contraception for those
participating in clinical studies.
- Has a negative highly sensitive pregnancy test ([urine or serum] as required
by local regulations) within [specify time frame eg, 72 hours] before the first
dose of study intervention. [If a urine test cannot be confirmed as negative
(eg, an ambiguous result), a serum pregnancy test is required. In such cases,
the participant must be excluded from participation if the serum pregnancy
result is positive.]
- Abstains from breastfeeding during the study intervention period and for at
least 120 days after study intervention.
- Medical history, menstrual history, and recent sexual activity has been
reviewed by the investigator to decrease the risk for inclusion of a woman with
an early undetected pregnancy.
10. The participant (or legally acceptable representative) has provided
documented informed
consent/assent for the study. The participant may also provide consent/assent
for FBR. However, the participant may participate in the study without
participating in FBR.
11. HIV-infected participants must have well controlled HIV on ART meeting all
of the criteria below:
a. Participants on ART must have a CD4+ T cell count >350 cells/mm3 at the time <br
The participant must be excluded from the study if the participant meets the
following criteria:
1. Has had chemotherapy, definitive radiation, or biological cancer therapy
within 4 weeks (2 weeks for palliative radiation) before the first dose of
study intervention or has not recovered to CTCAE Grade 1 or better from any AEs
that were due to cancer therapeutics administered more than 4 weeks earlier
(this includes participants with previous immunomodulatory therapy with
residual immune-related AEs). Participants receiving ongoing replacement
hormone therapy for endocrine immune-related AEs will not be excluded from
participation in this study.
2. Has a history of a second malignancy, unless potentially curative treatment
has been completed with no evidence of malignancy for 2 years. Note:
Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder,
that have undergone potentially curative therapy are not excluded.
3. Has clinically active CNS metastases and/or carcinomatous meningitis.
Participants with previously treated brain or meningeal metastases may
participate and be eligible for treatment provided they are stable and
asymptomatic (without evidence of progression by MRI scan of the brain
separated by at least 4 weeks after treatment), have no evidence of new or
enlarging brain metastases, are evaluated within 4 weeks before first study
intervention administration, and are off immunosuppressive doses of systemic
steroids at least 2 weeks before enrollment.
4. Has an active infection requiring therapy.
5. History of an allogenic stem cell transplant or a solid organ transplant.
6. Has a history of (noninfectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
7. Has an active autoimmune disease that has required systemic treatment in the
past 2 years (ie, with use of disease modifying agents, corticosteroids, or
immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy.
Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, is not considered a
form of systemic treatment and is allowed. Use of nonsystemic steroids is
permitted.
8. HIV-infected participants with a history of Kaposi*s sarcoma and/or
Multicentric Castleman*s Disease.
9. Has a history or current evidence of any condition, therapy, laboratory
abnormality, or other circumstance that might confound the results of the study
or interfere with the participant*s participation for the full duration of the
study, such that it is not in the best interest of the participant to
participate, in the opinion of the treating investigator.
10. Has known psychiatric or substance abuse disorders that would interfere
with the participant*s ability to cooperate with the requirements of the study.
11. Is pregnant or breastfeeding or expecting to conceive or father children
within the projected duration of the study, starting with the Screening Visit
through 120 days after the last dose of study intervention.
12. Has not fully recovered from any effects of major surgery without
significant detectable infection. Surgeries that required general anesthesia <br
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To determine the safety and tolerability and to establish a preliminary<br /><br>recommended Phase2 dose (RP2D) and/or an maximum tolerated dose (MTD) or an<br /><br>maximum administered dose(MAD) of MK-4464 administered via IV infusion as<br /><br>monotherapy and in combination with pembrolizumab IV infusion.<br /><br>Endpoints:<br /><br>• Dose-limiting toxicity (DLT)<br /><br>• Adverse event (AE)<br /><br>• Discontinuing study treatment due to an AE</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. To evaluate the PK of MK-4464 administered via IV infusion as monotherapy<br /><br>and in combination with pembrolizumab IV infusion.<br /><br>Endpoints:<br /><br>• Appropriate PK parameters of MK-4464, which may include Cmin, Cmax, and AUC<br /><br><br /><br>2. To evaluate ORR as assessed by the investigator per RECIST 1.1. RECIST 1.1<br /><br>is adjusted to follow a maximum of 10 target lesions and a maximum of 5 target<br /><br>lesions per organ.<br /><br>Endpoints:<br /><br>• Objective response: CR or PR</p><br>