Clinical trial NCT06445972: Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)
Official title: A Phase 1/2 Open-Label, Umbrella Platform Design Study to Evaluate the Safety and Efficacy of MK-2870 Plus Paclitaxel as the Second-Line Treatment of Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma: Substudy 06D
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastroesophageal Junction
Gastroesophageal Adenocarcinoma
Esophageal Neoplasms
Esophageal Cancer
Keywords: Programmed Cell Death 1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-06-06
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

Detailed description: This is a substudy of the master protocol MK-3475-U06 (KEYMAKER-U06).

Eligibility criteria: Inclusion Criteria:

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

* Has histologically and/or cytologically confirmed diagnosis of previously treated, 2L (received first line (1L) treatment) gastric adenocarcinoma, GEJ adenocarcinoma, or esophageal adenocarcinoma
* Has metastatic disease or locally advanced, unresectable disease
* Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy
* Participants with gastroesophageal adenocarcinoma that is known to be human epidermal growth factor receptor 2 (HER2)/neu positive are excluded. Participants with unknown HER2 status are eligible.
* Has provided an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion
* AEs due to previous anticancer therapies must be ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable.
* Has Eastern Cooperative Oncology Group performance status of 0 or 1
* Has a life expectancy of at least 3 months
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
* Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
* Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.

Exclusion Criteria:

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

* Has squamous cell or undifferentiated gastroesophageal cancer
* Has experienced weight loss \>20% over 3 months before the first dose of study intervention
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has Grade ≥2 peripheral neuropathy
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to randomization
* Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization
* Has uncontrolled arterial hypertension ≥150/≥90 mm mercury (Hg)
* Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
* Has undergone major surgery within 28 days prior to randomization, or central venous access device placement within 7 days prior to randomization or planned major surgery following initiation of study treatment
* Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents
* Is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs) or other antiplatelet agents
* Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization
* Has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry
* Has history of GI perforation and/or fistulae within 6 months prior to randomization
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC), topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1 inhibitor-based chemotherapy
* Has received any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor (VEGFR) signaling pathways
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study drug intervention
* Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active infection requiring systemic therapy
* Has a concurrent active HBV (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid) infection
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has severe hypersensitivity (Grade ≥3) to sacituzumab tirumotecan, any of its excipients and/or to another biologic therapy
* Has not adequately recovered from major surgery or have ongoing surgical complications

Primary outcomes:
measure: Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase
timeFrame: Up to ~28 days
measure: Percentage of Particiapants who Experience an Adverse Event (AE) During the Safety Lead-In Phase
timeFrame: Up to ~60 days
measure: Percentage of Participants who Discontinue Study Intervention Due to an AE During the Safety Lead-In Phase
timeFrame: Up to ~28 days
measure: Objective Response Rate (ORR)
timeFrame: Up to ~28 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to ~50 months
measure: Duration of Response (DOR)
timeFrame: Up to ~50 months
measure: Overall Survival (OS)
timeFrame: Up to ~50 months
measure: Percentage of Particiapants who Experience an AE During the Efficacy Phase
timeFrame: Up to ~50 months
measure: Percentage of Participants who Discontinue Study Intervention Due to an AE During the Efficacy Phase
timeFrame: Up to ~50 months
measure: Incidence of sacituzumab tirumotecan anti-drug antibody (ADA)
timeFrame: Up to ~50 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 8927)
state: Arizona
city: Louisville
country: United States
facility: Norton Cancer Institute - Downtown ( Site 8900)
state: Kentucky
city: Grand Rapids
country: United States
facility: The Cancer and Hematology Centers ( Site 8912)
state: Michigan
city: East Syracuse
country: United States
facility: Hematology-Oncology Associates of Central NY, P.C. ( Site 8925)
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 8907)
state: New York
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center-UPMC ( Site 8904)
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center ( Site 8920)
state: Texas
city: Natal.
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer ( Site 8303)
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição ( Site 8301)
state: Rio Grande Do Sul
city: Puerto Montt.
country: Chile
facility: Clínica Puerto Montt ( Site 8409)
state: Los Lagos
city: Talca
country: Chile
facility: Centro de Investigación del Maule ( Site 8408)
state: Maule
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 8400)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Centro de Oncología de Precisión-Oncology ( Site 8404)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica UC San Carlos de Apoquindo ( Site 8405)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill-Clinical Area ( Site 8401)
state: Region M. De Santiago
city: Antofagasta
country: Chile
facility: Bradford Hill Norte ( Site 8407)
city: Beijing
country: China
facility: Beijing Cancer hospital-Digestive Oncology ( Site 7500)
state: Beijing
city: Fuzhou
country: China
facility: The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 7501)
state: Fujian
city: XiaMen
country: China
facility: The First Affiliated hospital of Xiamen University ( Site 7503)
state: Fujian
city: Zhengzhou
country: China
facility: Henan Cancer Hospital ( Site 7504)
state: Henan
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University ( Site 7514)
state: Jiangxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 7513)
state: Shanghai
city: Urumqi
country: China
facility: Xinjiang Medical University Cancer Hospital - Urumqi ( Site 7506)
state: Xinjiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 7510)
state: Zhejiang
city: Brest
country: France
facility: Centre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologi ( Site 7104)
state: Finistere
city: Lille
country: France
facility: CIC. ( Site 7100)
state: Nord
city: Paris
country: France
facility: Pitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 7102)
city: Hamburg
country: Germany
facility: Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 8807)
city: Meldola
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 7207)
state: Emilia-Romagna
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 7200)
state: Lombardia
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Department of Oncology ( Site 7901)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Division of Hematology/Oncology ( Site 7900)
city: Oslo
country: Norway
facility: Oslo universitetssykehus, Radiumhospitalet ( Site 8501)
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG) ( Site 8701)
state: Geneve
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden-Medizin ( Site 8700)
state: Grisons
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 8007)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 8001)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital-Oncology ( Site 8000)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 8005)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: