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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06074588




Registration number
NCT06074588
Ethics application status
Date submitted
3/10/2023
Date registered
10/10/2023
Date last updated
27/06/2024

Titles & IDs
Public title
Sacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004)
Scientific title
A Randomized, Open-label, Phase 3 Study of MK-2870 vs Chemotherapy (Docetaxel or Pemetrexed) in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations
Secondary ID [1] 0 0
2023-503539-16
Secondary ID [2] 0 0
2870-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Sacituzumab tirumotecan
Treatment: Drugs - Docetaxel
Treatment: Drugs - Pemetrexed

Experimental: Sacituzumab tirumotecan - Participants will receive 4 mg/kg of sacituzumab tirumotecan via intravenous (IV) infusion on Days 1, 15 and 29 of each 6-week cycle. Additionally, participants receive diphenhydramine (or equivalent), an H2 antagonist of investigator's choice, acetaminophen (or equivalent), and dexamethasone (or equivalent) per each drug's product label prior to the first 4 infusions of sacituzumab tirumotecan. At subsequent infusions, the H2 antagonist and dexamethasone are optional, at the discretion of the investigator.

Active comparator: Chemotherapy - Participants will receive 75 mg/m\^2 of docetaxel or 500 mg/m\^2 of pemetrexed by IV infusion on Days 1 and 22 of every 6-week cycle.


Treatment: Other: Sacituzumab tirumotecan
4 mg/kg of MK-sacituzumab tirumotecan by IV infusion

Treatment: Drugs: Docetaxel
75 mg/m\^2 of docetaxel by IV Infusion

Treatment: Drugs: Pemetrexed
500 mg/m\^2 of pemetrexed by IV infusion
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) of Participants with NSCLC with Epidermal Growth Factor Receptor (EGFR) Mutations
Timepoint [1] 0 0
Up to approximately 35 months
Primary outcome [2] 0 0
Overall Survival (OS) of Participants with NSCLC with EGFR mutations
Timepoint [2] 0 0
Up to approximately 41 months
Secondary outcome [1] 0 0
PFS of All Participants with NSCLC
Timepoint [1] 0 0
Up to approximately 35 months
Secondary outcome [2] 0 0
OS of All Participants with NSCLC
Timepoint [2] 0 0
Up to approximately 41 months
Secondary outcome [3] 0 0
Objective Response Rate (ORR) of Participants with NSCLC with EGFR Mutations
Timepoint [3] 0 0
Up to approximately 35 months
Secondary outcome [4] 0 0
ORR of All Participants with NSCLC
Timepoint [4] 0 0
Up to approximately 35 months
Secondary outcome [5] 0 0
Duration of Response (DOR) of All Participants with NSCLC
Timepoint [5] 0 0
Up to approximately 6 years
Secondary outcome [6] 0 0
Change in Score from Baseline in Global Health Status/QoL Score (European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Items 29 and 30)
Timepoint [6] 0 0
Baseline and up to approximately 48 weeks
Secondary outcome [7] 0 0
Change in Score from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)
Timepoint [7] 0 0
Baseline and up to approximately 48 weeks
Secondary outcome [8] 0 0
Change in Score from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)
Timepoint [8] 0 0
Baseline and up to approximately 48 weeks
Secondary outcome [9] 0 0
Change in Score from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)
Timepoint [9] 0 0
Baseline and up to approximately 48 weeks
Secondary outcome [10] 0 0
Time to Deterioration (TTD) from Baseline in Global Health Status/QoL Score (EORTC QLQ-C30 Items 29 and 30)
Timepoint [10] 0 0
Up to approximately 48 weeks
Secondary outcome [11] 0 0
TTD from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)
Timepoint [11] 0 0
Up to approximately 48 weeks
Secondary outcome [12] 0 0
TTD from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)
Timepoint [12] 0 0
Up to approximately 48 weeks
Secondary outcome [13] 0 0
Time to Deterioration from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)
Timepoint [13] 0 0
Up to approximately 48 weeks
Secondary outcome [14] 0 0
Number of Participants Who Experience One or More Adverse Events (AEs)
Timepoint [14] 0 0
Up to approximately 6 years
Secondary outcome [15] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [15] 0 0
Up to approximately 4 years

Eligibility
Key inclusion criteria
The main inclusion and exclusion criteria include but are not limited to the following:



* Histologically- or cytologically-documented advanced (Stage III not eligible for resection or curative radiation) or metastatic non-squamous NSCLC with specific mutations.
* Documentation of locally assessed radiological disease progression while on or after last treatment based on Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1.
* Participants with genome mutations must have received 1 or 2 prior lines of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), including a third generation TKI for participants with a T790M mutation; and 1 platinum-based therapy after progression on or after EGFR TKI.
* Measurable disease per RECIST 1.1 as assessed by the local site investigator.
* Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided
* Participants who have AEs due to previous anticancer therapies must have recovered to Grade =1 or baseline.
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
* Have an ECOG performance status of 0 or 1 within 3 days before randomization.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has predominantly squamous cell histology NSCLC.
* Has mixed tumor(s) with small cell elements.
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
* Has Grade =2 peripheral neuropathy.
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
* Has an EGFR T790M mutation and has not received a third generation EGFR TKI (eg, osimertinib).
* Received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) before randomization.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
* Received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention.
* Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC).
* Received prior treatment with a topoisomerase I-containing ADC.
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
* Known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Active infection requiring systemic therapy.
* History of noninfectious pneumonitis/ILD that required steroids or has current pneumonitis/ILD.
* Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks, and are off steroids 3 days prior to dosing with study medication.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
11/03/2030
Actual
Sample size
Target
556
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St. George Private Hospital ( Site 3004) - Kogarah
Recruitment hospital [2] 0 0
Westmead Hospital-Department of Medical Oncology ( Site 3000) - Westmead
Recruitment hospital [3] 0 0
Monash Health-Oncology Research ( Site 3001) - Clayton
Recruitment hospital [4] 0 0
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 3003) - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3021 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Mississippi
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Chile
State/province [7] 0 0
Araucania
Country [8] 0 0
Chile
State/province [8] 0 0
Maule
Country [9] 0 0
Chile
State/province [9] 0 0
Region M. De Santiago
Country [10] 0 0
Chile
State/province [10] 0 0
Valparaiso
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Chongqing
Country [13] 0 0
China
State/province [13] 0 0
Fujian
Country [14] 0 0
China
State/province [14] 0 0
Guangdong
Country [15] 0 0
China
State/province [15] 0 0
Guangxi
Country [16] 0 0
China
State/province [16] 0 0
Hubei
Country [17] 0 0
China
State/province [17] 0 0
Hunan
Country [18] 0 0
China
State/province [18] 0 0
Shaanxi
Country [19] 0 0
China
State/province [19] 0 0
Shanghai
Country [20] 0 0
China
State/province [20] 0 0
Yunnan
Country [21] 0 0
China
State/province [21] 0 0
Zhejiang
Country [22] 0 0
Hong Kong
State/province [22] 0 0
Central
Country [23] 0 0
Hong Kong
State/province [23] 0 0
Hksar
Country [24] 0 0
Hong Kong
State/province [24] 0 0
Kowloon
Country [25] 0 0
Hong Kong
State/province [25] 0 0
Lai Chi Kok
Country [26] 0 0
Israel
State/province [26] 0 0
Haifa
Country [27] 0 0
Israel
State/province [27] 0 0
Jerusalem
Country [28] 0 0
Israel
State/province [28] 0 0
Petah Tikva
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Chungbuk
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Jeonranamdo
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Kyonggi-do
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Kyongsangnam-do
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Pusan-Kwangyokshi
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Taejon-Kwangyokshi
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Malaysia
State/province [36] 0 0
Kelantan
Country [37] 0 0
Malaysia
State/province [37] 0 0
Kuala Lumpur
Country [38] 0 0
Malaysia
State/province [38] 0 0
Sarawak
Country [39] 0 0
Taiwan
State/province [39] 0 0
Changhua
Country [40] 0 0
Taiwan
State/province [40] 0 0
Kaohsiung
Country [41] 0 0
Taiwan
State/province [41] 0 0
Tainan
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei
Country [43] 0 0
Taiwan
State/province [43] 0 0
Hsinchu
Country [44] 0 0
Thailand
State/province [44] 0 0
Chiang Mai
Country [45] 0 0
Thailand
State/province [45] 0 0
Khon Kaen

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate sacituzumab tirumotecan versus chemotherapy (docetaxel or pemetrexed) for the treatment of previously-treated non-small cell lung cancer (NSCLC) with exon 19del or exon 21 L858R EGFR mutations (hereafter referred to as EGFR mutations or EGFR-mutated) or any of the follow genomic alterations: ALK gene rearrangements, ROS1 rearrangements, BRAF V600E mutations, NTRK gene fusions, MET exon 14 skipping mutations, RET rearrangements, or less common EGFR point mutations of exon 20 S768I, exon 21 L861Q, or exon 18 G719X mutations. The primary hypotheses are that sacituzumab tirumotecan is: (1) superior to chemotherapy with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by BICR in NSCLC with EGFR mutations; and (2) superior to chemotherapy with respect to overall survival (OS) in NSCLC with EGFR mutations.
Trial website
https://clinicaltrials.gov/study/NCT06074588
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06074588