Tumor, Solid
Conditions
Brief summary
This study of the safety, tolerability, and efficacy of MK-8353 (formerly SCH 900353) given as single agent oral therapy for participants with advanced solid tumors will be done into two parts. In Part 1a, there will be a dose escalation to find the preliminary maximum tolerated dose (MTD), and in Part 1b, dose confirmation to find out the recommended Phase 2 dose (RPTD) that will be used in Part 2 of the study. In Part 2 of the study, participants with certain types of metastatic melanoma or metastatic colorectal cancer will be treated to see if MK-8353 is effective as single agent therapy.
Interventions
DRUGMK-8353
Administered orally twice daily for 28 days for each cycle
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically/histologically confirmed solid tumor (metastatic or locally advanced disease) that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. * Participants of childbearing potential must have negative pregnancy test; females and males must agree to use effective contraception during the course of the trial and for 90 days after stopping study drug. * For Part 1b and Part 2, participant with metastatic melanoma or metastatic colorectal cancer with at least one measurable lesion * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with a life expectancy of ≥3 months. * Adequate organ function.
Exclusion criteria
* Unstable or progressing central nervous system (CNS) metastasis unless asymptomatic for 3 months, with no need for steroids or antiseizure medications. * Active gastrointestinal disease or a disorder or a history of surgery that significantly alters gastrointestinal motility or absorption. * Has not recovered from previous therapy and had any chemotherapy, biologic, or hormonal therapy within 4 weeks of study enrollment. * Radiation therapy (except palliative radiation to bone lesions) within 4 weeks of study enrollment. * More than 3 prior regimens of chemotherapy, biologic therapy, hormonal therapy, or investigational drugs not including adjuvant or neoadjuvant treatments. * Clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic diseases. * Mean QTcF interval (interval on the electrocardiogram corrected for heart rate using Fridericia's correction) \> 450 msec at baseline. * Known Human Immunodeficiency Virus (HIV) infection, hepatitis infection, or tuberculosis infection. * Current participation in any other interventional clinical study. * History of significant eye disease, including glaucoma, retinopathy, or retinal vein occlusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) | Cycles of 28 days, up to approximately 9 months treatment and a 30-day follow-up period for a total time of up to approximately 10 months | DLT was derived from the toxicities observed during the first cycle (28 days) for each dose level. DLT is defined as any hematologic or non-hematologic toxicity ≥Grade 3 as pre-specified per protocol, or drug-related toxicity, regardless of Common Terminology Criteria for Adverse Events (CTCAE) grade that causes \>20% of the intended total number of doses in Cycle 1 to be missed. |
| Number of Participants With Overall Response Rate | Baseline, and every 8 weeks until disease progression or discontinuation from study up to approximately 10 months | Overall Response rate is defined as the number of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
Participant flow
Recruitment details
25 participants were enrolled, received at least 1 dose of MK-8353 and were included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| MK-8353 100 mg Twice Daily (BID) Participants received 100 mg twice daily for 28 days during each cycle | 2 |
| MK-8353 200 mg BID Participants received 200 mg twice daily for 28 days during each cycle | 3 |
| MK-8353 300 mg BID Participants received 300 mg twice daily for 28 days during each cycle | 4 |
| MK-8353 350 mg BID Participants received 350 mg twice daily for 28 days during each cycle | 3 |
| MK-8353 400 mg BID Participants received 400 mg twice daily for 28 days during each cycle | 7 |
| MK-8353 800 mg BID Participants received 800 mg twice daily for 28 days during each cycle | 6 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Events | 1 | 1 | 1 | 0 | 1 | 5 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Participants did not wish to continue | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progress of disease under investigation | 1 | 2 | 3 | 1 | 3 | 0 |
| Overall Study | Symptomatic Deterioration | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | MK-8353 100 mg Twice Daily (BID) | MK-8353 200 mg BID | MK-8353 300 mg BID | MK-8353 350 mg BID | MK-8353 400 mg BID | MK-8353 800 mg BID | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 5.7 | 49.3 years STANDARD_DEVIATION 11.4 | 62.5 years STANDARD_DEVIATION 8.4 | 64.3 years STANDARD_DEVIATION 9 | 59.3 years STANDARD_DEVIATION 9.3 | 59.8 years STANDARD_DEVIATION 9 | 59.5 years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 1 Participants | 4 Participants | 3 Participants | 7 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 1 / 3 | 1 / 4 | 0 / 3 | 1 / 7 | 2 / 6 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 4 / 4 | 3 / 3 | 7 / 7 | 6 / 6 |
| serious Total, serious adverse events | 1 / 2 | 1 / 3 | 1 / 4 | 1 / 3 | 3 / 7 | 5 / 6 |
Outcome results
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs)
DLT was derived from the toxicities observed during the first cycle (28 days) for each dose level. DLT is defined as any hematologic or non-hematologic toxicity ≥Grade 3 as pre-specified per protocol, or drug-related toxicity, regardless of Common Terminology Criteria for Adverse Events (CTCAE) grade that causes \>20% of the intended total number of doses in Cycle 1 to be missed.
Time frame: Cycles of 28 days, up to approximately 9 months treatment and a 30-day follow-up period for a total time of up to approximately 10 months
Population: Analysis population includes all participants who received at least one dose of MK-8353 and completed Cycle 1 of Part 1 or discontinued due to toxicity. Participants who discontinued treatment due to reasons other than toxicity were not included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Maculopapular Rash | 0 Participants |
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Diarrhea | 0 Participants |
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 fatigue | 0 Participants |
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 nausea/vomiting/diarrhea | 0 Participants |
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 4 | 0 Participants |
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 5 | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Diarrhea | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 nausea/vomiting/diarrhea | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 5 | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Maculopapular Rash | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 fatigue | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 4 | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 5 | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 4 | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 nausea/vomiting/diarrhea | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 fatigue | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Maculopapular Rash | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Diarrhea | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 nausea/vomiting/diarrhea | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Diarrhea | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 fatigue | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 5 | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 4 | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Maculopapular Rash | 0 Participants |
| MK-8353 400 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Maculopapular Rash | 1 Participants |
| MK-8353 400 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 4 | 0 Participants |
| MK-8353 400 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Diarrhea | 1 Participants |
| MK-8353 400 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 fatigue | 0 Participants |
| MK-8353 400 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 nausea/vomiting/diarrhea | 0 Participants |
| MK-8353 400 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 5 | 0 Participants |
| MK-8353 800 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 nausea/vomiting/diarrhea | 1 Participants |
| MK-8353 800 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 fatigue | 1 Participants |
| MK-8353 800 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 4 | 0 Participants |
| MK-8353 800 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 5 | 0 Participants |
| MK-8353 800 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Diarrhea | 0 Participants |
| MK-8353 800 mg BID | Number of Participants With Dose-Limiting Toxicities (DLTs) | Grade 3 Maculopapular Rash | 0 Participants |
Primary
Number of Participants With Overall Response Rate
Overall Response rate is defined as the number of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: Baseline, and every 8 weeks until disease progression or discontinuation from study up to approximately 10 months
Population: The analysis population is defined as all participants who received at least 1 dose of MK-8353 and had at least 1 post-baseline efficacy assessment. Participants who received at least one dose but had no post-baseline assessment were counted as not evaluable and were not included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Overall Response Rate | Partial Response | 0 Participants |
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Overall Response Rate | Partial Response Unconfirmed | 0 Participants |
| MK-8353 100 mg Twice Daily (BID) | Number of Participants With Overall Response Rate | Complete Response | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Overall Response Rate | Partial Response | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Overall Response Rate | Partial Response Unconfirmed | 0 Participants |
| MK-8353 200 mg BID | Number of Participants With Overall Response Rate | Complete Response | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Overall Response Rate | Partial Response Unconfirmed | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Overall Response Rate | Complete Response | 0 Participants |
| MK-8353 300 mg BID | Number of Participants With Overall Response Rate | Partial Response | 1 Participants |
| MK-8353 350 mg BID | Number of Participants With Overall Response Rate | Partial Response Unconfirmed | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Overall Response Rate | Complete Response | 0 Participants |
| MK-8353 350 mg BID | Number of Participants With Overall Response Rate | Partial Response | 1 Participants |
| MK-8353 400 mg BID | Number of Participants With Overall Response Rate | Partial Response Unconfirmed | 1 Participants |
| MK-8353 400 mg BID | Number of Participants With Overall Response Rate | Complete Response | 0 Participants |
| MK-8353 400 mg BID | Number of Participants With Overall Response Rate | Partial Response | 0 Participants |
| MK-8353 800 mg BID | Number of Participants With Overall Response Rate | Partial Response | 0 Participants |
| MK-8353 800 mg BID | Number of Participants With Overall Response Rate | Complete Response | 0 Participants |
| MK-8353 800 mg BID | Number of Participants With Overall Response Rate | Partial Response Unconfirmed | 0 Participants |