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NCT Number: NCT06074588

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)

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 hypothesis is that sacituzumab tirumotecan is superior to chemotherapy with respect to overall survival (OS) in NSCLC with EGFR mutations.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Non-small Cell Lung Cancer (NSCLC) Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

St. George Private Hospital ( Site 3004), Kogarah, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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, radiologically stable for at least 4 weeks and do not require glucocorticoids for at least 14 days prior to randomization.
  • 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.

Treatment and study plan

Sacituzumab tirumotecan

Biological

4 mg/kg of MK-sacituzumab tirumotecan by IV infusion

Other names: SKB264, MK-2870

docetaxel

Drug

75 mg/m^2 of docetaxel by IV Infusion

Other names: TAXOTERE®

Pemetrexed

Drug

500 mg/m^2 of pemetrexed by IV infusion

Other names: ALIMTA®

Primary outcomes

  1. Overall Survival (OS) of Participants with NSCLC with Epidermal Growth Factor Receptor (EGFR) Mutations

    Time frame: Up to approximately 41 months

    OS is defined as the time from randomization to death due to any cause.

Secondary outcomes

  1. OS of All Participants with NSCLC

    Time frame: Up to approximately 41 months

    OS is defined as the time from randomization to death due to any cause.

  2. Progression-free Survival (PFS) of Participants with NSCLC with EGFR Mutations

    Time frame: Up to approximately 41 months

    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.

  3. PFS of All Participants with NSCLC

    Time frame: Up to approximately 41 months

    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.

  4. Objective Response Rate (ORR) of Participants with NSCLC with EGFR Mutations

    Time frame: Up to approximately 35 months

    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.

  5. ORR of All Participants with NSCLC

    Time frame: Up to approximately 35 months

    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.

  6. Duration of Response (DOR) of All Participants with NSCLC

    Time frame: Up to approximately 6 years

    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.

  7. 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)

    Time frame: Baseline and up to approximately 48 weeks

    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.

  8. Change in Score from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)

    Time frame: Baseline and up to approximately 48 weeks

    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.

  9. Change in Score from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)

    Time frame: Baseline and up to approximately 48 weeks

    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.

  10. Change in Score from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)

    Time frame: Baseline and up to approximately 48 weeks

    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.

  11. Time to Deterioration (TTD) from Baseline in Global Health Status/QoL Score (EORTC QLQ-C30 Items 29 and 30)

    Time frame: Up to approximately 48 weeks

    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.

  12. TTD from Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8)

    Time frame: Up to approximately 48 weeks

    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.

  13. TTD from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer 13 [QLQ-LC13] Item 31)

    Time frame: Up to approximately 48 weeks

    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.

  14. Time to Deterioration from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40)

    Time frame: Up to approximately 48 weeks

    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.

  15. Number of Participants Who Experience One or More Adverse Events (AEs)

    Time frame: Up to approximately 6 years

    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.

  16. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

    Time frame: Up to approximately 4 years

    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.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2027
Study completion
2030
First posted
Oct 10, 2023
Registry last updated
Jul 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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