Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 3
Merck Sharp & Dohme LLC (Voir sur ClinicalTrials)
novembre 2023
mars 2030
28 décembre 2024
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/12/2024 12:44:10 | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CENTRE LEON BERARD ( Site 1305) - 69373 - Lyon Cedex08 - Rhone-Alpes - France | Study Coordinator | Contact (sur clinicalTrials) | |||
| Institut Bergonié - Centre Régional de Lutte Contre Le Cance-Medical Oncology ( Site 1303) - 33076 - Bordeaux - Aquitaine - France | Study Coordinator | Contact (sur clinicalTrials) | |||
| Institut Curie-Thorax Institute ( Site 1304) - 75248 - Paris - France | Study Coordinator | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
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.