A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001)

NCT03918278 | Completed Phase 1 FDA Drug

• 5 other identifiers: 0482-001MK-0482-0012022-500821-34-00U1111-1278-27662020-004089-20
• Study Type: interventional
• Target: 222
• Locations: 8 countries
• Sites: 16

Brief Summary

This is a 2 part study. Part 1 is a dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) dose of MK-0482 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors for which there is no available therapy which may convey clinical benefit. Part 2 is expansion cohort to determine safety and tolerability of MK-0482 in combination with pembrolizumab with and without chemotherapy in participants with advanced tumor specific cohorts.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 1 only)

  DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for \>1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; \>2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing \>25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.

  Cycle 1 (Up to 21 days)

• Number of Participants Who Experience at Least One Adverse Event (AE)

  An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.

  Up to approximately 27 months

• Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

  The number of participants who discontinue study treatment due to an AE will be presented.

  Up to approximately 24 months

• Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 2 only)

  DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for \>1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; \>2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing \>25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.

  Up to approximately 28 days from the start of study intervention

Secondary Outcomes (8)

• Minimum Serum Concentration (Cmin) of MK-0482 When Administered as Monotherapy (Part 1 only)

  At designated time points (Up to approximately 25 months)

• Cmin of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)

  At designated time points (Up to approximately 25 months)

• Maximum Serum Concentration (Cmax) of MK-0482 When Administered as Monotherapy (Part 1 only)

  At designated time points (Up to approximately 25 months)

• Cmax of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)

  At designated time points (Up to approximately 25 months)

• Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered as Monotherapy (Part 1 only)

  At designated time points (Up to approximately 25 months)

Study Arms (7)

Part 1: MK-0482 Monotherapy

EXPERIMENTAL

Participants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).

Biological: MK-0482

Part 1: MK-0482 + Pembrolizumab Combination Therapy

EXPERIMENTAL

Participants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).

Biological: MK-0482; Biological: pembrolizumab

Part 2: Cohort A

EXPERIMENTAL

Participants with metastatic triple negative breast cancer (TNBC) first line treatment (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) and paclitaxel 90 mg/m\^2 via IV infusion until PD or discontinuation.

Biological: MK-0482; Biological: pembrolizumab; Drug: Paclitaxel

Part 2: Cohort B

EXPERIMENTAL

Participants with recurrent non-operable glioblastoma (GBM) current treatment of second line (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).

Biological: MK-0482; Biological: pembrolizumab

Part 2: Cohort C

EXPERIMENTAL

Participants with metastatic pancreatic ductal adenocarcinoma (PDAC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years), Nab-Paclitaxel 125 mg/m\^2 via IV infusion and gemcitabine 1000 mg/m\^2 via IV infusion until PD or unacceptable toxicity that requires discontinuation.

Biological: MK-0482; Biological: pembrolizumab; Drug: Nab-paclitaxel; Drug: Gemcitabine

Part 2: Cohort D

EXPERIMENTAL

Participants with metastatic soft tissue sarcoma (STS) (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).

Biological: MK-0482; Biological: pembrolizumab

Part 2: Cohort E

EXPERIMENTAL

Participants with metastatic non-squamous non-small cell lung carcinoma (NSCLC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion plus Pemetrexed 500 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) plus carboplatin with desired dose of area under the curve (AUC) 5 and pemetrexed 500 mg/m\^2, both administered via IV infusion, followed by maintenance therapy with pemetrexed 500 mg/m\^2 via IV infusion for up to a total of 35 administrations (up to approximately 2 years).

Biological: MK-0482; Biological: pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed

Interventions

MK-0482 BIOLOGICAL

IV infusion

Part 1: MK-0482 + Pembrolizumab Combination Therapy; Part 1: MK-0482 Monotherapy; Part 2: Cohort A; Part 2: Cohort B; Part 2: Cohort C; Part 2: Cohort D; Part 2: Cohort E

pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Part 1: MK-0482 + Pembrolizumab Combination Therapy; Part 2: Cohort A; Part 2: Cohort B; Part 2: Cohort C; Part 2: Cohort D; Part 2: Cohort E

Paclitaxel DRUG

IV infusion

Also known as: Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol

Part 2: Cohort A

Nab-paclitaxel DRUG

IV infusion

Also known as: Abraxane

Part 2: Cohort C

Gemcitabine DRUG

IV infusion

Also known as: Gemzar

Part 2: Cohort C

Carboplatin DRUG

IV infusion

Also known as: Paraplatin ®

Part 2: Cohort E

Pemetrexed DRUG

IV infusion

Also known as: Alimta

Part 2: Cohort E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1 only: Has histologically-or cytologically-confirmed advanced/metastatic solid tumors and have received, been intolerant to, or been ineligible for, all treatments known to confer clinical benefit
• Has measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for Cohort B as assessed by the local site investigator/radiology
• Has provided an evaluable archival or newly obtained tumor tissue sample
• Part 1, Arm 1 only: Has ≥1 discrete malignant lesions that are amenable to biopsy
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Male participants are eligible to participate if they agree to the following during the intervention period and for at least 95 days after the last dose of chemotherapy: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or agree to use contraception unless confirmed to be azoospermic
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and ≥1 of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 180 days after the last dose of chemotherapy or 120 days after the last dose of MK-0482 or pembrolizumab, whichever occurs last
• Part 2 Cohort A, C, and E only: WOCBP must also agree not to donate to others or freeze/store for her own use for the purpose of reproduction during and for at least 180 days after the last dose of chemotherapy
• Has a negative highly sensitive pregnancy test within 72 hours before the first dose of study treatment
• Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on anti-retroviral therapy (ART)
• Has adequate organ function
• Part 2 Cohort A only: 1) Has histologically confirmed locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) 2) Has received no prior systemic therapy for metastatic TNBC 3) Has tumor programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥1
• Part 2 Cohort B only: 1) Has confirmed diagnosis of GBM (isocitrate dehydrogenase (IDH) wildtype per 2021 World Health Organization (WHO) classification of tumors of central nervous system) 2) Has received a standard first-line treatment for GBM including surgery and radiation therapy with or without chemotherapy and evidence of disease recurrence or pression by magnetic resonance imaging (MRI) 3) Has time elapsed from prior treatment as per protocol 4) Has Karnofsky performance status (KPS) ≥ 80 within 7 days before start of study treatment 5) Is neurologically stable 6) Has known status of O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH)
• Part 2 Cohort C only: Has histologically confirmed diagnosis of metastatic PDAC and has received no prior systemic therapy for metastatic pancreatic ductal adenocarcinoma (PDAC) including chemotherapy, biological or targeted therapy and has albumin ≥3.0 g/dL
• Part 2 Cohort D only: Has histologically confirmed diagnosis of locally advanced or metastatic soft tissue sarcoma (STS) and has received and progressed after one prior line of systemic treatment for advanced STS. Prior treatment in the (neo)adjuvant setting is not counted as a line of treatment for advanced disease

You may not qualify if:

• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years; with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
• Has known active central nervous system metastases and/or carcinomatous meningitis
• Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or any component of pembrolizumab (MK-3475) or MK-0482
• Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
• Has an active infection requiring systemic therapy
• Has a history of interstitial lung disease
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has known Hepatitis B or C infection
• Has received prior systemic anticancer therapy, definitive radiotherapy, including investigational agents within 4 weeks (2 weeks for palliative radiation) before the first dose of study treatment
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study treatment
• Has received an investigational agent or has used an investigational device 4 weeks prior to start of study intervention
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (16)

Henry Ford Health System ( Site 0002)

Detroit, Michigan, 48202, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0003)

Hackensack, New Jersey, 07601, United States

Location

Next Oncology ( Site 0001)

San Antonio, Texas, 78229, United States

Location

Macquarie University ( Site 0033)

Macquarie University, New South Wales, 2109, Australia

Location

Alfred Health ( Site 0031)

Melbourne, Victoria, 3004, Australia

Location

BC Cancer - Vancouver Center ( Site 0010)

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Princess Margaret Cancer Centre ( Site 0011)

Toronto, Ontario, M5G 2M9, Canada

Location

FALP-UIDO ( Site 0100)

Santiago, Region M. de Santiago, 6900941, Chile

Location

Bradfordhill-Clinical Area ( Site 0101)

Santiago, Region M. de Santiago, 8420383, Chile

Location

Hadassa Ein Karem Medical Center ( Site 0022)

Jerusalem, 9112001, Israel

Location

Chaim Sheba Medical Center ( Site 0020)

Ramat Gan, 5265601, Israel

Location

ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0091)

Siena, Tuscany, 53100, Italy

Location

Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (

Milan, 20141, Italy

Location

Seoul National University Hospital ( Site 0061)

Seoul, 03080, South Korea

Location

Asan Medical Center ( Site 0060)

Seoul, 05505, South Korea

Location

Hospital Clinic i Provincial ( Site 0041)

Barcelona, 08036, Spain

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab; Paclitaxel; Taxes; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; Carboplatin; Pemetrexed

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 17, 2019
• Study Start: June 19, 2019
• Primary Completion: June 9, 2025
• Study Completion: June 9, 2025
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); IL (2); US (3); AU (2); KR (2); CL (2); CA (2); ES (1)