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NeoplasmsPhase 1NCT02972034

Study of MK-8353 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Malignancies (MK-8353-013)

A Phase 1 study testing MK-8353 and Pembrolizumab in people with Neoplasms and Colorectal Cancer, run by Merck Sharp & Dohme LLC at 3 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will evaluate the safety, tolerability and preliminary efficacy of MK-8353 when administered in combination with pembrolizumab (MK-3475). There are two parts in this study: Part 1 will be dose escalation and confirmation, and Part 2 will be a cohort expansion. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Colorectal Cancer
What is being tested?
MK-8353 and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
3 sitesin 2 countries
Study dates
13 Jan 2017to 2 Dec 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part 1: Has a histologically- or cytologically-documented, locally-advanced or metastatic solid malignancy and has received ≥1 and <6 prior line of cancer treatment regimen(s).
  • Part 2: Has a histologically-confirmed adenocarcinoma originating from the colon or rectum (Stage 4 American Joint Committee on Cancer [AJCC] 7th edition) that is microsatellite stable (i.e., non-MSI-H/dMMR). Appendiceal cancer is included AND Has experienced disease progression or was intolerant to at least 1 and up to 5 systemic chemotherapy regimen(s) for metastatic CRC that must have included fluroropyrimidines and irinotecan or oxaliplatin, ± anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR)(if indicated by RAS mutational status).
  • Provides an archival or newly obtained tumor tissue sample and blood samples for biomarker analysis.
  • Has ≥1 measurable lesion as defined by RECIST 1.1 on imaging studies.
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Has adequate organ function
  • Female participants of childbearing potential who are willing to use either 2 adequate barrier methods, or to abstain from heterosexual activity throughout the study.
  • Male participants of childbearing potential must agree to use an adequate method of contraception.

Who cannot join

  • Has disease that is suitable for local treatment administered with curative intent.
  • Part 1: Has received prior therapy with cancer vaccines, or compounds targeting PD-1 (including Merck pembrolizumab [MK-3475]), programmed cell death ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or Mitogen-activated protein kinase (MAPK)/Extracellular signal-regulated Kinase (MEK).
  • Part 2: Has received prior therapy with cancer vaccines, or compounds targeting PD-1 (including Merck pembrolizumab [MK-3475]), PD-L1, PD-L2, CTLA-4, lymphocyte-activation gene 3 (LAG-3), CD-137, OX-40 (tumor necrosis factor receptor superfamily, member 4 [TNFRSF4], also known as CD134), cluster of differentiation 40 (CD-40), glucocorticoid-induced TNFR-related protein (GITR), serine/threonine-protein kinase B-Raf (BRAF), MEK or other molecules in the MAPK pathway.
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of study drug.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Has had a prior anticancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or has not recovered (i.e. ≤ Grade 1 or at Baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier.
Show all 19Show fewer
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to a previously administered agent.
  • Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors within 4 weeks prior to study Day 1.
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a history of interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  • Has a known history of Human Immunodeficiency Virus (HIV).
  • Has known active Hepatitis B or Hepatitis C.
  • Has received a live-virus vaccination within 30 days of planned treatment start.
  • Has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Call for Information (Investigational Site 0002)

    Grand Rapids, Michigan, 49546

  • Call for Information (Investigational Site 0001)

    Nashville, Tennessee, 37203

Other trials in United States

Canada1 site

  • Merck Canada

    Kirkland, Quebec, H9H 4M7

Other trials in Canada

About this study

Official title: A Phase Ib Study to Evaluate the Safety and Tolerability of MK-8353 in Combination With Pembrolizumab in Patients With Advanced Malignancies

This study will evaluate the safety, tolerability and preliminary efficacy of MK-8353 when administered in combination with pembrolizumab (MK-3475). There are two parts in this study: Part 1 will be dose escalation and confirmation, and Part 2 will be a cohort expansion. In Part 1, the recommended phase II dose (RP2D) of MK-8353 in combination with a fixed dose of pembrolizumab in participants with advanced malignancies will be identified and confirmed. Participants will be initially enrolled to receive MK-8353 at 350 mg twice a day (BID) in combination with pembrolizumab at a fixed dose of 200 mg on Day 1 of each 3-week cycle (Q3W) for up to 24 months of treatment. In Part 2, participants with advanced colorectal cancer (CRC) that is microsatellite stable (i.e., non-microsatellite instability-high/deficient mismatch repair [non-MSI-H/dMMR]) who received at least one and up to five prior lines of therapy will be enrolled at the RP2D in the expansion cohort to further evaluate safety and efficacy.

Being tested
MK-8353, Pembrolizumab
Medical subject headings
Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-8353Drug

    PO capsule

  • PembrolizumabBiological

    Also called MK-3475

    IV infusion

Study groups in NCT02972034
Study groupRoleWhat they receive
A: MK-8353 BID Continuous+PembroExperimentalParticipants receive MK-8353 orally (PO) two times each day (BID) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab (pembro) 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 35 cycles.
Receives: Drug: MK-8353; Biological: Pembrolizumab
B: MK-8353 QD Continuous+PembroExperimentalParticipants receive MK-8353 PO once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
Receives: Drug: MK-8353; Biological: Pembrolizumab
C: MK-8353 QD 1 Week On/1 Week Off+PembroExperimentalOptional Arm: Participants receive MK-8353 PO QD on Days 1 to 7, Days 15 to 21 and Days 29 to 35 PLUS pembrolizumab 200 mg IV on Day 1 and Day 22 of each 42-day period (based on 2 cycles of 21 days) for up to 35 cycles.
Receives: Drug: MK-8353; Biological: Pembrolizumab
D: MK-8353 QD Run-in→MK-8353 QD Continuous+PembroExperimentalOptional Arm: Participants undergo an MK-8353 PO QD run-in period from Day -14 to Day -1 prior to Cycle 1 during which they receive MK-8353 PO QD. After the run-in period, participants receive MK-8353 PO QD on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 36 cycles.
Receives: Drug: MK-8353; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced an Adverse Event (AE)

    Number of participants who experienced an AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment

    Measured: Up to 27 months

  2. Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.

    Measured: Up to 24 months

  3. Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)

    DLT was defined as a treatment-related adverse event (AE) including the following: Grade (Gr) 4 nonhematologic toxicity (not laboratory), Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with clinically significant bleeding, Gr 3 non-hematological AE with the exception of fatigue lasting >3 days despite optimal supportive care, any Gr 3 or Gr 4 nonhematologic laboratory value if medical intervention is required to treat the subject, or abnormality leads to hospitalization or abnormality persists for >1 week, Gr 3 or Gr 4 febrile neutropenia, prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity, any treatment-related toxicity that causes the subject to discontinue treatment during Cycle 1, missing >25% of MK-8353 doses as a result of drug-related AE(s) during the first cycle, Gr 5 toxicity.

    Measured: Cycle 1 (Arms A, B & C: Up to 21 days)

Secondary outcomes (4)

  1. Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator

    ORR was defined as the percentage of the participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator was presented.

    Measured: Up to 24 months

  2. Percent Change in Cancer Antigen 125 (CA-125)

    CA-125 was the tumour biomarker used to test cancer. Disease progression is indicated by CA-125 tumor marker elevation.

    Measured: Cycle 1-8 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days.

  3. Percent Change in Carcinoembryonic Antigen (CEA)

    CEA was the tumour biomarker used to test cancer. Disease progression is indicated by CEA tumor marker elevation.

    Measured: Cycle 1-9 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days

  4. Percent Change in Carbohydrate Antigen (CA19-9)

    CA19-9 was the tumour biomarker used to test cancer. Disease progression is indicated by CA19-9 tumor marker elevation

    Measured: Cycle 1-7 Day 1, and end of treatment/ safety follow-up (30 days after the last dose). Each cycle was 21 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2016 (estimated)
  2. Study start13 Jan 2017
  3. Primary completion2 Dec 2022
  4. Study completion2 Dec 2022

Why it stopped: business reasons.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02972034
Sponsor's protocol ID
8353-013
Other IDs
MK-8353-013, 2016-003478-42, 2016
Status last verified
Nov 2024
First submitted
21 Nov 2016
Last updated
21 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Lakhani NJ, Burris H 3rd, Miller WH Jr, Huang M, Chen LC, Siu LL. A phase 1b study of the ERK inhibitor MK-8353 plus pembrolizumab in patients with advanced solid tumors. Invest New Drugs. 2024 Oct;42(5):581-589. doi: 10.1007/s10637-024-01461-z. Epub 2024 Sep 14.

    PubMed 39276176

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-8353 and Pembrolizumab in people with Neoplasms and Colorectal Cancer, run by Merck Sharp & Dohme LLC at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced an Adverse Event (AE) (time frame: Up to 27 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02972034, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2024.

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