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)

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06074588
• Other study ID #: 2870-004
• Secondary ID: 2023-503539-16jR
• Status: Recruiting
• Phase: Phase 3
• Start date: November 12, 2023
• Est. completion date: March 11, 2030

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 556
• Est. completion date: March 11, 2030
• Est. primary completion date: May 10, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Inclusion Criteria:

• 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.

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Biological:
• Sacituzumab tirumotecan
4 mg/kg of MK-sacituzumab tirumotecan by IV infusion

Drug:
• Docetaxel
75 mg/m^2 of docetaxel by IV Infusion
• Pemetrexed
500 mg/m^2 of pemetrexed by IV infusion

Locations

Country	Name	City	State
Australia	Monash Health-Oncology Research ( Site 3001)	Clayton	Victoria
Australia	St. George Private Hospital ( Site 3004)	Kogarah	New South Wales
Australia	Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 3003)	Melbourne	Victoria
Australia	Westmead Hospital-Department of Medical Oncology ( Site 3000)	Westmead	New South Wales
Canada	William Osler Health System ( Site 0205)	Brampton	Ontario
Canada	Princess Margaret Cancer Centre ( Site 0204)	Toronto	Ontario
Chile	Bradfordhill-Clinical Area ( Site 0507)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 0509)	Santiago	Region M. De Santiago
Chile	Orlandi Oncologia-Oncology ( Site 0504)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 0502)	Santiago	Region M. De Santiago
Chile	Clinica Universidad Catolica del Maule-Oncology ( Site 0501)	Talca	Maule
Chile	ONCOCENTRO APYS-ACEREY ( Site 0500)	Viña del Mar	Valparaiso
China	Chongqing University Cancer Hospital-Medical Oncology ( Site 2814)	Chongqing	Chongqing
China	Fujian Cancer Hospital ( Site 2819)	Fuzhou	Fujian
China	Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine (	Guangzhou	Guangdong
China	Yunnan Province Cancer Hospital ( Site 2824)	Kunming	Yunnan
China	Guangxi Medical University Cancer Hospital-Respiratory Oncology ( Site 2816)	Nanning	Guangxi
China	Shanghai Chest Hospital-Oncology department ( Site 2800)	Shanghai	Shanghai
China	Hubei Cancer Hospital ( Site 2809)	Wuhan	Hubei
China	Tongji Hospital Tongji Medical,Science & Technology ( Site 2805)	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University-Oncology ( Site 2817)	Xi'an	Shaanxi
Hong Kong	Hong Kong Integrated Oncology Centre ( Site 3200)	Central
Hong Kong	Queen Mary Hospital ( Site 3203)	Hksar
Hong Kong	Queen Elizabeth Hospital-Department of Clinical Oncology ( Site 3204)	Kowloon
Hong Kong	Princess Margaret Hospital-Department of Oncology ( Site 3201)	Lai Chi Kok
Israel	Rambam Health Care Campus-Oncology Division ( Site 1702)	Haifa
Israel	Shaare Zedek Medical Center ( Site 1700)	Jerusalem
Israel	Rabin Medical Center ( Site 1703)	Petah Tikva
Korea, Republic of	Pusan National University Hospital ( Site 3805)	Busan	Pusan-Kwangyokshi
Korea, Republic of	Chungbuk National University Hospital-Internal medicine ( Site 3809)	Cheongju-si	Chungbuk
Korea, Republic of	National Cancer Center-Lung Cancer Center ( Site 3810)	Goyang-si	Kyonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital-Pulmonology ( Site 3807)	Hwasun	Jeonranamdo
Korea, Republic of	Chungnam national university hospital ( Site 3808)	Jung-gu	Taejon-Kwangyokshi
Korea, Republic of	Seoul National University Bundang Hospital ( Site 3806)	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 3801)	Seoul
Korea, Republic of	Kangbuk Samsung Hospital ( Site 3813)	Seoul
Korea, Republic of	Konkuk University Medical Center ( Site 3812)	Seoul
Korea, Republic of	Korea University Guro Hospital-Internal Medicine ( Site 3800)	Seoul
Korea, Republic of	Samsung Medical Center-Division of Hematology/Oncology ( Site 3802)	Seoul
Korea, Republic of	The Catholic University Of Korea St. Vincent's Hospital-Medical Oncology ( Site 3803)	Suwon-si	Kyonggi-do
Korea, Republic of	Pusan National University Yangsan Hospital-Lung Cancer Clinic ( Site 3811)	Yangsan	Kyongsangnam-do
Malaysia	Hospital Raja Perempuan Zainab II-Medical Department ( Site 3502)	Kota Bharu	Kelantan
Malaysia	Sarawak General Hospital-Radiotherapy Unit ( Site 3500)	Kuching	Sarawak
Malaysia	National Cancer Institute-Radiotherapy and Oncology ( Site 3504)	Putrajaya	Kuala Lumpur
Taiwan	Changhua Christian Hospital ( Site 3908)	Changhua County	Changhua
Taiwan	National Taiwan University Hospital - Hsinchu branch ( Site 3907)	Hsinchu
Taiwan	E-Da hospital ( Site 3911)	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 3912)	Kaohsiung
Taiwan	Chang Gung Memorial Hospital at Kaohsiung ( Site 3906)	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	National Cheng Kung University Hospital ( Site 3909)	Tainan
Taiwan	Chi Mei Medical Center ( Site 3910)	Tainan City	Tainan
Taiwan	Mackay Memorial Hospital-Chest Medicine ( Site 3902)	Taipei
Taiwan	National Taiwan University Hospital-Oncology ( Site 3904)	Taipei
Taiwan	Taipei Medical University Hospital ( Site 3900)	Taipei
Taiwan	National Taiwan University Cancer Center (NTUCC) ( Site 3903)	Taipei City	Taipei
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 4003)	Chiang Mai
Thailand	Faculty of Medicine - Khon Kaen University ( Site 4004)	Khon Kaen
United States	Hattiesburg Clinic Hematology/Oncology ( Site 0010)	Hattiesburg	Mississippi
United States	Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0003)	Marietta	Georgia
United States	Mid Florida Hematology and Oncology Center ( Site 0005)	Orange City	Florida
United States	Capital Health Medical Center - Hopewell ( Site 0006)	Pennington	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  China,  Hong Kong,  Israel,  Korea, Republic of,  Malaysia,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) of Participants with NSCLC with Epidermal Growth Factor Receptor (EGFR) Mutations	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.	Up to approximately 35 months
Primary	Overall Survival (OS) of Participants with NSCLC with EGFR mutations	OS is defined as the time from randomization to death due to any cause.	Up to approximately 41 months
Secondary	PFS of All Participants with NSCLC	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first.	Up to approximately 35 months
Secondary	OS of All Participants with NSCLC	OS is defined as the time from randomization to death due to any cause.	Up to approximately 41 months
Secondary	Objective Response Rate (ORR) of Participants with NSCLC with EGFR Mutations	ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. based on BICR in NSCLC with EGFR mutations.	Up to approximately 35 months
Secondary	ORR of All Participants with NSCLC	ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. based on BICR in all participants with NSCLC.	Up to approximately 35 months
Secondary	Duration of Response (DOR) of All Participants with NSCLC	For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR in all participants with NSCLC, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 6 years
Secondary	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)	The EORTC QLQ-C30 is a questionnaire to assess the overall health status and quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status and quality of life. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.	Baseline and up to approximately 48 weeks
Secondary	Change in Score from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. The change from baseline in the dyspnea (EORTC QLQ-C30 Item 8) score will be presented.	Baseline and up to approximately 48 weeks
Secondary	Change in Score from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome.	Baseline and up to approximately 48 weeks
Secondary	Change in Score from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. A lower score indicates a better outcome.	Baseline and up to approximately 48 weeks
Secondary	Time to Deterioration (TTD) from Baseline in Global Health Status/QoL Score (EORTC QLQ-C30 Items 29 and 30)	The EORTC QLQ-C30 is a questionnaire to assess the overall health status and quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status and quality of life. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Items 29 and 30 will be presented.	Up to approximately 48 weeks
Secondary	TTD from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Item 8 will be presented.	Up to approximately 48 weeks
Secondary	TTD from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate more frequent coughing and a worse outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-LC13 Item 31 will be presented.	Up to approximately 48 weeks
Secondary	Time to Deterioration from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-LC13 Item 40 will be presented.	Up to approximately 48 weeks
Secondary	Number of Participants Who Experience One or More Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention whether or not considered related to the study intervention.	Up to approximately 6 years
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention whether or not considered related to the study intervention.	Up to approximately 4 years

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary