A Phase 1 Study of MK-5890 as Monotherapy and in Combination with Pembrolizumab in Participants with Advanced Solid Tumors
- Conditions
- advanced/metastatic solid tumors10027655
- Registration Number
- NL-OMON52475
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 51
1. a) Dose Escalation/Confirmation Phase (Arms 1 and 2): 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.
b) Dose Escalation/Confirmation Phase (Arm 3): Have a histologically or
cytologically confirmed diagnosis of stage IV non-squamous NSCLC.
c) Dose Expansion Phase (Arm 2a): Have a diagnosis of TNBC. Participants must
have received or been intolerant to not more than 2 lines of therapy for
metastatic disease known to confer clinical benefit. Prior therapy should have
included anthracycline and/or taxane for early-stage or metastatic disease.
Participants must have lactate dehydrogenase (LDH) <=2 x ULN at screening.
Enrollment will be capped at a maximum of 7-10 participants who are PD-1/PD-L1
inhibitor treatment-refractory.
d) Dose Expansion Phase (Arm 1a, 2b, and 2c): Have a diagnosis of endometrial
cancer. Participants must have received or been intolerant to no more than 2
prior lines of treatment known to confer clinical benefit. Prior therapy should
have included platinum-containing regimens for early-stage or metastatic
disease. Enrollment will be capped at a maximum of 5-7 participants per
treatment arm who are PD-1/PD-L1 inhibitor treatment-refractory.
e) Dose Expansion Phase (Arm 4): Have TNBC with tumor PD-L1 CPS<10, that is
either locally recurrent, inoperable, not previously treated with chemotherapy
and which cannot be treated with curative intent or metastatic disease not
previously treated with chemotherapy.
2. Have measureable disease by RECIST 1.1. as assessed by the local site
investigator/radiologist. Target lesions situated in a previously irradiated
area are considered measurable if progression has been demonstrated in such
lesions.
3. Have adequate organ function as defined in the protocol. Specimens must be
collected within 7 days before the first dose of study treatment.
4. Be male or non-pregnant and non-breast feeding female, >18 years of age on
the day of signing informed consent.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1.
6. A male participant must agree to use contraception during the treatment
period and for at least 120 days after the last dose of MK-5890 or
pembrolizumab OR 180 days after the last dose of chemotherapeutic agents and
refrain from donating sperm during this period.
7. A female participant is eligible to participate if she is not pregnant , not
breastfeeding, and at least one of the following conditions applies:
a.) She is not a woman of childbearing potential (WOCBP)
OR
b.) She is a WOCBP who agrees to follow the contraceptive guidance during the
treatment period and for at least 120 days after the last dose of MK-5890 or
pembrolizumab OR 180 days after the last dose of chemotherapeutic agents.
8. The participant (or legally acceptable representative if applicable)
provides documented informed consent/assent for the study. The participant may
also provide consent/assent for Future Biomedical Research, however he/she may
participate in the main study without participating in Future Biomedical
Research.
9. Submit an evaluable baseline tumor sample for analysis (either a newly
obtained or archival tumor sample). Formalin-fixed, p
1. Has a history of a second malignancy, unless potentially curative treatment
has been completed with no evidence of malignancy for 2 years.
Note: The time requirement does not apply to the disease under study,
participants who underwent successful definitive resection of basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder
cancer, in situ cervical cancer, or other in situ cancers.
2. Has clinically active central nervous system (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 magnetic
resonance imaging [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 the start of study treatment, and are off
immunosuppressive doses of systemic steroids for at least 2 weeks prior to
enrollment.
3. Has had a severe hypersensitivity reaction to treatment with a mAb and/or
other components of the study treatment.
4. Has an active infection requiring systemic treatment.
5. Has a history of interstitial lung disease.
6. Has a history of (noninfectious) pneumonitis that required steroids or
current pneumonitis.
7. Has symptomatic ascites or pleural effusion. Participants who are clinically
stable after treatment of these conditions (including therapeutic
thoracocentesis or paracentesis) will not be excluded from participation in
this study.
8. Has previously had a stem cell or bone marrow transplant.
9. Has previously had a solid organ transplant.
10. 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.
11. Has known human immunodeficiency virus ([HIV]; HIV 1 or 2 antibodies)
and/or active and acute Hepatitis B or C infections (eg, positive for HBsAg/HBV
DNA or HCV RNA).
12. Has a 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 treatments 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.
13. Has not fully recovered from any effects of major surgery without
significant detectable infection. Surgeries that required general anesthesia
must be completed at least 2 weeks before the start of study treatment.
Surgeries that required regional/epidural anesthesia must be completed at least
72 hours before the first dose of study treatment and participants should be
recovered.
14. Has known psychiatric or substance abuse disorders that would interfere
with the participant*s ability to cooperate with the requirements
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Number of participants with a dose-limiting toxicity (DLT)<br /><br>- Number of participants with >=1 adverse event (AE)<br /><br>- Number of participants who discontinue study treatment due to an AE</p><br>
- Secondary Outcome Measures
Name Time Method <p>PK parameters including area under the curve (AUC), minimum concentration<br /><br>(Cmin), and maximum concentration (Cmax)</p><br>