KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)

Official title

KEYMAKER-U01 Substudy 01A: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab With or Without Chemotherapy in Treatment-Naive Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)

Overview

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, MK-0482, I-DXd, or HER3-DXd in treatment-naïve participants with advanced squamous or non-squamous NSCLC. This study is one of the pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Detailed description

The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

Interventions

• Biological Pembrolizumab
  IV infusion
• Drug Carboplatin
  IV infusion
• Drug Paclitaxel
  IV infusion
• Drug Pemetrexed
  IV infusion
• Biological Vibostolimab
  IV infusion
• Biological Boserolimab
  IV infusion
• Biological MK-4830
  IV infusion
• Biological MK-0482
  IV Infusion
• Biological Ifinatamab Deruxtecan (I-DXd)
  IV infusion
• Biological HER3-DXd
  IV Infusion

Primary outcome measures

• Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Time frame: Up to approximately 24 months]
• Part B: Number of Participants Who Experience One or More Adverse Events (AEs) [Time frame: Up to approximately 27 months]
• Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE) [Time frame: Up to approximately 24 months]
• Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [Time frame: Up to approximately 3 Weeks]

Secondary outcome measures (11)

• Part A: Progression-Free Survival (PFS) According to RECIST 1.1 [Time frame: Up to approximately 24 months]
• Part A: Number of Participants Who Experience One or More AEs [Time frame: Up to approximately 27 months]
• Part A: Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 24 months]
• Part B: ORR per RECIST 1.1 as assessed by blinded independent central review (BICR) [Time frame: Up to approximately 24 months]
• Part B: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR [Time frame: Up to approximately 24 months]
• Part B: Cmax of I-DXd [Time frame: At designated time points up to approximately 2 years]
• Part B: Cmax of HER3-DXd [Time frame: At designated time points up to approximately 2 years]
• Part B: Cmax of pembrolizumab [Time frame: At designated time points up to approximately 2 years]
• Part B: Ctrough of I-DXd [Time frame: At designated time points up to approximately 2 years]
• Part B: Ctrough of HER3-DXd [Time frame: At designated time points up to approximately 2 years]
• Part B: Ctrough of pembrolizumab [Time frame: At designated time points up to approximately 2 years]

Eligibility criteria

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

• Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or nonsquamous NSCLC
• Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy
• Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
• Has not received prior systemic treatment for their metastatic NSCLC
• Is able to complete all screening procedures within the 35-day screening window for Part A and 28-day screening window for Part B

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

• Has a diagnosis of small cell lung cancer
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment administration, or New York Heart Association Class III or IV congestive heart failure
• Has a known history of human immunodeficiency virus (HIV) infection. Well-controlled HIV with anti-retroviral therapy (ART) is not excluded
• Has a known history of Hepatitis B (HPV) or known active Hepatitis C virus infection. Hepatitis B surface antigen (HBsAg) positive is eligible if on HBV antiviral therapy for at least 4 weeks and HBV viral load is undetectable prior to randomization
• Has had major surgery <3 weeks before the first dose of study treatment
• Is expected to require any other form of antineoplastic therapy while on study
• Has a history or current evidence of a gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
• Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis
• Has preexisting neuropathy that is moderate in intensity
• Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
• Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed
• Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients
• Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
• Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
• Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
• Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
• Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
• Has had an allogenic tissue/solid organ transplant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 18 centers

• Banner MD Anderson Cancer Center ( Site 0001) — Gilbert
• City of Hope ( Site 0014) — Duarte
• UCSF Medical Center at Mission Bay ( Site 0007) — San Francisco
• Georgetown University ( Site 0036) — Washington D.C.
• University of Kentucky Markey Cancer Center ( Site 0019) — Lexington
• MedStar Franklin Square Medical Center ( Site 0033) — Baltimore
• Massachusetts General Hospital ( Site 0003) — Boston
• Dana Farber Cancer Institute ( Site 0002) — Boston
• … and 10 more centers

Israel · 7 centers

• Soroka Medical Center ( Site 0072) — Beersheba
• Rambam Health Care Campus-Oncology ( Site 0076) — Haifa
• Shaare Zedek Medical Center ( Site 0075) — Jerusalem
• Meir Medical Center ( Site 0071) — Kfar Saba
• Rabin Medical Center ( Site 0074) — Petah Tikva
• Chaim Sheba Medical Center ( Site 0070) — Ramat Gan
• Sourasky Medical Center ( Site 0077) — Tel Aviv

Ukraine · 4 centers

• COMMUNAL NONPROFIT ENTERPRISE CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND — Cherkasy
• Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Surgery department #2 ( Site — Ivano-Frankivsk
• ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0461) — Rivne
• Uzhhorod Multispecialty City Clinical Hospital ( Site 0462) — Uzhhorod

Hungary · 3 centers

• Petz Aladar Megyei Oktato Korhaz ( Site 0062) — Győr
• Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061) — Szolnok
• Orszagos Koranyi Pulmonologiai Intezet ( Site 0060) — Budapest

Italy · 3 centers

• Azienda Ospedaliera Universitaria Careggi ( Site 0173) — Florence
• IRCCS Ospedale San Raffaele ( Site 0171) — Milan
• Policlinico Gemelli di Roma ( Site 0174) — Roma

Poland · 3 centers

• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Kl — Warsaw
• Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150) — Gdansk
• Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site — Koszalin

South Korea · 3 centers

• Seoul National University Bundang Hospital ( Site 0081) — Seongnam-si
• Severance Hospital ( Site 0080) — Seoul
• Samsung Medical Center ( Site 0082) — Seoul

Taiwan · 3 centers

• Changhua Christian Hospital ( Site 0181) — Changhua
• Taipei Medical University Hospital ( Site 0180) — Taipei
• Chang Gung Medical Foundation-Linkou Branch ( Site 0182) — Taoyuan

Spain · 2 centers

• ICO L Hospitalet ( Site 0090) — L'Hospitalet de Llobregat
• Hospital Universitario Quiron Madrid ( Site 0091) — Madrid

Identifiers

NCT: NCT04165070 · 3475-01A · MK-3475-01A · KEYMAKER-U01A · 2023-506932-33-00 · U1111-1294-6474 · 2020-001626-56

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗