Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001)

  • STATUS
    Recruiting
  • End date
    Nov 18, 2024
  • participants needed
    410
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 4 May 2022
paclitaxel
measurable disease
carcinoma
breast cancer
growth factor
lung cancer
dental caries
treatment regimen
x-rays
metastasis
pemetrexed
carboplatin
pembrolizumab
HER2
EGFR
cetuximab
pd-l1
trastuzumab
primary cancer
cancer chemotherapy
antineoplastic agents
adenocarcinoma
solid tumor
metastatic solid tumor
solid neoplasm
immunostimulants
metastatic malignant solid tumor

Summary

This study has dose escalation (Part A, B, C) and dose expansion (Cohorts A-L) parts. Dose escalation is to evaluate the safety, tolerability, and preliminary efficacy of MK-4830 monotherapy administration (Parts A and B) and in combination with pembrolizumab (Part C). Dose expansion is to evaluate the objective response rate (ORR) of MK-4830 in combination with pembrolizumab and evaluate the safety, tolerability and ORR of MK-4830 administered in combination with pembrolizumab and chemotherapy. There is no formal hypothesis testing in this study.

Details
Condition Neoplasms
Treatment cisplatin, carboplatin, Paclitaxel, Pembrolizumab, Pemetrexed, Lenvatinib, MK-4830
Clinical Study IdentifierNCT03564691
SponsorMerck Sharp & Dohme Corp.
Last Modified on4 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Dose escalation participants: Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and has received, has been intolerant to, or has been ineligible for all treatment known to confer clinical benefit. Solid tumors of any type are eligible for enrollment
Has measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), Response Assessment in Neuro-Oncology (RANO), or modified RECIST (mRECIST) as assessed by the local site investigator/radiology
Submits an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample)
Dose Escalation Part C and Back-fill participants: Has 1 or more discrete malignant lesions that are amenable to biopsy
Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. This inclusion criterion does not apply to Expansion phase Arm B
Demonstrates adequate organ function
A male participant must agree to use an approved contraception(s) during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) OR if a WOCBP agrees to follow the study contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment
Expansion phase Arm A participants
Has histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
Received at least 1 prior line of therapy and no more than 3 prior lines of systemic therapy
Expansion phase Arm B participants
Has histologically or cytologically confirmed unresectable glioblastoma multiforme (GBM) or its variants
Has a Karnofsky performance status (KPS) ≥ 70
Has had no more than 1 prior line of therapy for GBM. Radiation with or without chemotherapy is acceptable as the prior treatment
Has shown unequivocal evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan by contrast within 2 weeks prior to randomization
Has an interval of at least 3 weeks (to randomization) between prior surgical resection (one week for stereotactic biopsy)
Has an interval of at least 12 weeks from the completion of radiation therapy to randomization unless there is unequivocal histologic confirmation of tumor progression or radiographic progression outside of the prior radiation field
Is neurologically stable (eg, without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable
Expansion phase Arm C participants
Has histologically confirmed recurrent or metastatic head and neck squamous cell cancer (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
Has experienced disease progression at any time during or after treatment with a platinum-containing (eg, carboplatin or cisplatin) regimen with or without cetuximab
Expansion phase Arm D participants
Has histologically confirmed advanced or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
Should not have had any prior programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) therapy
Expansion phase Arms E and F participants
Has a histologically or cytologically confirmed diagnosis of Advanced (Stage IIIb) or Stage IV metastatic non-small-cell lung cancer (NSCLC)
Has received no prior systemic therapy for chemotherapy or other targeted or biological antineoplastic therapy treatment for Stage IIIb or Stage IV metastatic NSCLC. Treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed if therapy was completed at least 6 months prior to the diagnosis of advanced disease. Participants with prior treatment with an anti-PD-1 or PD-L1 agent are not eligible
Expansion phase Arm G participants
Has a histologically or cytologically confirmed diagnosis of Advanced (Stage IIIb) or Stage IV metastatic non-squamous NSCLC (American Joint Committee on Cancer (AJCC) version 8)
Is able to tolerate chemotherapy with carboplatin and pemetrexed
Has received no prior systemic therapy for advanced NSCLC
Expansion phase Arm H participants
Has histologically confirmed diagnosis of renal cell cancer (RCC) with clear cell component with or without sarcomatoid features
Has locally advanced/metastatic disease or has recurrent disease
Has received no prior systemic therapy for advanced RCC
Expansion phase Arm I participants
Has histologically confirmed diagnosis of recurrent and/or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies
Has received and progressed on at least two prior chemotherapy regimens
If tumor was if human epidermal growth factor receptor 2 (HER2/neu) positive, participant must have previously received treatment with trastuzumab
Expansion phase Arm J participants
Must have histologically confirmed high-grade epithelial ovarian, fallopian tube or primary peritoneal carcinoma
Has received prior systemic therapy
Has radiographic evidence of disease progression
Is a candidate for paclitaxel chemotherapy
Expansion phase Arm K participants
Have locally recurrent inoperable breast cancer OR have metastatic breast cancer not previously treated
Have centrally confirmed triple-negative breast cancer (TNBC)
Have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months elapsed between the completion of treatment and first documented local or distant disease recurrence
Have been treated with (neo)adjuvant anthracycline
Expansion phase Arm L participants
Have histologically confirmed diagnosis of recurrent and/or advanced mesothelioma that is considered incurable by standard therapies
Be eligible to receive standard chemotherapy

Exclusion Criteria

Has not recovered from all radiation-related toxicities to Grade 1 or less, requires corticosteroids, and had radiation pneumonitis
Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
Has known untreated central nervous system metastases or known carcinomatous meningitis. This exclusion criterion does not apply to Expansion phase Arm B
Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related AEs
Has an active infection requiring therapy
Has a history of noninfectious pneumonitis that required steroids or current pneumonitis
Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy
Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure
Known history of human immunodeficiency virus (HIV)
Known active hepatitis B or C
Is taking chronic systemic steroids in doses >10 mg daily of prednisone or equivalent within 7 days prior to the first dose of trial treatment
Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier
Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of MK-4830
All Expansion phase participants
Tumor types with known MSI-high status are not eligible
Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of pembrolizumab and/or chemotherapy agents
Expansion phase Arm A participants
Has received more than 3 lines of prior therapy for advanced disease (pancreatic cancer)
Has a history or current interstitial lung disease
Expansion phase Arm B participants
Has tumor primarily localized to the brainstem or spinal cord
Has presence of diffuse leptomeningeal disease or extracranial disease
Has recurrent tumor greater than 6 cm in maximum diameter
Requires treatment with moderate or high dose systemic corticosteroids for at least 3 days within 2 weeks of randomization
Expansion phase Arm D participants
Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their advanced metastatic HNSCC
Has not fully recovered from any effects of major surgery without significant detectable infection. Surgical proceduress that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered
Expansion phase Arm E and F participants
Has received a live or live-attenuated virus vaccine within 30 days prior to first dose of study intervention
Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their Stage IIIb or Stage IV metastatic NSCLC
Expansion phase Arm G participants
Has had prior treatment with any anti-PD-1, PD-L1, or programmed cell death-ligand 2 (PD-L2) agent
Expansion phase Arm H participants
Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their Stage IIIb or Stage IV non-squamous NSCLC
Has had prior treatment with any anti-PD-1, PD-L1, or PD-L2 agent
Has a clinically significant gastrointestinal (GI) abnormality
Has a history of untreated deep vein thrombosis or pulmonary embolism within 6 months prior to screening
Has poorly controlled hypertension
Has active GI bleeding
Has evidence of inadequate wound healing
Has active bleeding disorder or other history of significant bleeding episodes within 30 days prior to randomization
Has hemoptysis within 6 weeks prior to randomization
Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
Expansion phase Arm I participants
Has experienced weight loss > 10 % over 2 months prior to first dose of study therapy
Has clinical evidence of ascites
Has peritoneal metastases
Has received prior systemic anticancer therapy for advanced RCC with a tyrosine kinase inhibitor
Expansion phase Arm J participants
Has non-epithelial cancers, including borderline, malignant Müllerian mixed mucinous, malignant Brenner's tumor and undifferentiated carcinoma and/or germ cell tumors and/or sex cord - stromal tumors
Has received more than 2 prior lines of systemic therapy for ovarian cancer
Expansion phase Arm K participants
Has a known history of hypersensitivity or allergy to the study chemotherapies and/or any of their components
Expansion phase Arm L participants
Has a known history of hypersensitivity or allergy to the study chemotherapies and/or any of their components
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