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JOURNAL ONKOLOGIE – STUDIE

A Study to Assess Efficacy and Safety of Pembrolizumab With or Without Sacituzumab Tirumotecan (MK- 2870) in Adult Participants With Resectable Non Small Cell Lung Cancer (NSCLC) Not Achieving Pathological Complete Response (pCR) (MK-2870-019)

Rekrutierend

NCT-Nummer:
NCT06312137

Studienbeginn:
April 2024

Letztes Update:
08.08.2024

Wirkstoff:
Sacituzumab tirumotecan, Pembrolizumab, Cisplatin, Pemetrexed, Gemcitabine, Carboplatin, Paclitaxel

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 30)

Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0017)
60126 Elmhurst
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 630-527-3788» Ansprechpartner anzeigen
The Catholic University Of Korea St. Vincent's Hospital-Medical Oncology ( Site 1001)
16247 Suwon-si
Korea, Republic ofRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 82-31-249-8455» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

This study will assess if adding sacituzumab tirumotecan with pembrolizumab after surgery

is effective in treating NSCLC for participants not achieving pathological complete

response. The primary hypothesis of this study is sacituzumab tirumotecan plus

pembrolizumab is superior to pembrolizumab monotherapy with respect to disease free

survival (DFS) as assessed by blinded independent central review (BICR).

Ein-/Ausschlusskriterien

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

Inclusion Criteria:

- Has histological or cytological confirmation of squamous or nonsquamous non-small

cell lung cancer (NSCLC), resectable clinical Stage II, IIIA or IIIB (with nodal

involvement [N2]) per AJCC eighth edition guidelines.

- Has confirmation that epidermal growth factor receptor (EGFR)-directed therapy is

not indicated as primary therapy.

- Is able to undergo surgery based on opinion of investigator after consultation with

surgeon.

- Is able to receive neoadjuvant pembrolizumab and platinum-based doublet

chemotherapy.

- Applies to screening for the adjuvant period only, before randomization: Has not

achieved pathological complete response (pCR) at surgery by local review of

pathology.

- Applies to screening for the adjuvant period only, before randomization: Tumor

tissue sample from surgical resection has been provided for determination of

programmed cell death ligand 1 (PD-L1) and trophoblast cell surface antigen 2

(TROP2) status by central vendor before randomization into the adjuvant period.

- Applies to screening for the adjuvant period only, before randomization: Confirmed

to be disease-free based on re-baseline radiological assessment as documented by

contrast enhanced chest/abdomen/pelvis computed tomography (CT) (or magnetic

resonance imaging (MRI)) within 28 days before randomization.

- Participants who have AEs due to previous anticancer therapies must have recovered

to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately

treated with hormone replacement are eligible.

- Human immunodeficiency virus (HIV)-infected participants must have well controlled

HIV on antiretroviral therapy (ART).

- 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 at screening.

- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV

viral load is undetectable at least 4 weeks before the start of study intervention.

Exclusion Criteria:

- Has one of the following tumor locations/types:

- NSCLC involving the superior sulcus

- Large cell neuro-endocrine cancer (LCNEC)

- Sarcomatoid tumor

- Diagnosis of SCLC or, for mixed tumors, presence of small cell elements

- Documentation by local test report indicating presence of anaplastic lymphoma

kinase (ALK) gene rearrangements

- 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 active inflammatory bowel disease requiring immunosuppressive medication or

previous history of inflammatory bowel disease.

- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease,

including New York Heart Association Class III or IV congestive heart failure,

unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia,

prolongation of QT corrected for heart rate by Fridericia's cube root formula (QTcF)

interval to >480 ms, and/or other serious cardiovascular and cerebrovascular

diseases within the 6 months preceding study intervention.

- Has received prior neoadjuvant therapy for their current NSCLC diagnosis.

- Has received prior systemic anticancer therapy including investigational agents

within 4 weeks before the first dose of study intervention.

- Has received prior radiotherapy within 2 weeks of start of study intervention, or

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 diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of

immunosuppressive therapy within 7 days prior the first dose of study medication.

- Has a known additional malignancy that is progressing or has required active

treatment within the past 5 years.

- Has an active autoimmune disease that has required systemic treatment in the past 2

years.

- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required

steroids or has current pneumonitis/interstitial lung disease.

- Has an active infection requiring systemic therapy.

- Is an HIV-infected participant with a history of Kaposi's sarcoma and/or

Multicentric Castleman's Disease.

- Has a concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV

deoxyribonucleic acid (DNA)) and Hepatitis C virus (defined as anti-HCV antibody

(Ab) positive and detectable HCV ribonucleic acid (RNA)) infection.

- Has a severe hypersensitivity (Grade ≥3) to sacituzumab tirumotecan, any of its

excipients and/or to another biologic therapy.

- Has a history of allogeneic tissue/solid organ transplant.

- Has not adequately recovered from major surgery or have ongoing surgical

complications.

Studien-Rationale

Primary outcome:

1. Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR) (Time Frame - Up to ~ 93 months):
DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.



Secondary outcome:

1. Overall Survival (OS) (Time Frame - Up to ~ 118 months):
OS is defined as the time from randomization to death due to any cause.

2. Distant metastasis-free survival (DMFS) as assessed by investigator (Time Frame - Up to ~ 118 months):
DMFS is defined as the time from randomization to the first documented distant metastasis or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes.

3. Disease-Free Survival (DFS) as assessed by investigator (Time Frame - Up to ~ 118 months):
DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first.

4. Lung Cancer Specific Survival (LCSS) (Time Frame - Up to ~ 118 months):
LCSS is defined as the time from randomization to the date of death due to lung cancer.

5. Number of Participants Who Experience at least One Adverse Event (AE) (Time Frame - Up to ~ 118 months):
An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

6. Number of Participants Who Discontinue Study Intervention Due to AEs (Time Frame - Up to ~ 118 months):
An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an AE will be presented.

7. Change from Baseline in Global Health Status/Quality of Life (QoL) score (Quality of Life Questionnaire (QLQ)-C30 Items 29 and 30) (Time Frame - Baseline and up to ~118 months):
The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) is a psychometrically and clinically validated instrument appropriate for assessing the health-related quality of life (HRQoL) of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for the global health status or QoL a higher value indicates a better level of function.

8. Change from Baseline in Physical Functioning Score (QLQ-C30 Items 1 to 5) (Time Frame - Baseline and up to ~118 months):
The EORTC-QLQ is a psychometrically and clinically validated instrument appropriate for assessing the HRQoL of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for all physical functional scales, a higher value indicates a better level of function.

9. Change from Baseline in Role Functioning Score (QLQ-C30 Items 6 and 7) (Time Frame - Baseline and up to ~118 months):
The EORTC-QLQ is a psychometrically and clinically validated instrument appropriate for assessing the HRQoL of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for all role functional scales, a higher value indicates a better level of function.

10. Change from Baseline in Dyspnea scores (QLQ-C30 Item 8) (Time Frame - Baseline and up to ~118 months):
The EORTC-QLQ is a psychometrically and clinically validated instrument appropriate for assessing the HRQoL of cancer patients in oncology studies. Each scale or item is scored between 0 and 100, for symptom scales such as dyspnea, a higher value indicates increased severity of symptoms.

11. Change from Baseline in Coughing scores (QLQ-LC24 Items 31 and 52) (Time Frame - Baseline and up to ~118 months):
The lung cancer module of the EORTC, QLQ-LC24 is a revised and updated version of the Lung Cancer Module QLQ-LC13 and is a supplementary lung cancer specific module to be used along with EORTC QLQ C30. The QLQ-LC24 incorporates 4 multi-item scales to assess coughing, shortness of breath, hair problems, and fear of progression, for symptom scales as for cough, a higher value indicates increased severity of symptoms.

12. Change from Baseline in Chest pain scores (QLQ-LC24 Item 40) (Time Frame - Baseline and up to ~118 months):
The lung cancer module of the EORTC, QLQ-LC24 is a revised and updated version of the Lung Cancer Module QLQ-LC13 and is a supplementary lung cancer specific module to be used along with EORTC QLQ C30. The QLQ-LC24 incorporates 4 multi-item scales to assess coughing, shortness of breath, hair problems, and fear of progression, for symptom scales as for chest pain, a higher value indicates increased severity of symptoms.

Studien-Arme

  • Experimental: Pembrolizumab + Sacituzumab tirumotecan
    Participants will receive pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W) for up to 12 weeks + double-platinum chemotherapy per neoplasm histology classification at the investigator's discretion as neoadjuvant therapy prior to surgery; followed by sacituzumab tirumotecan 4 mg/kg IV infusion every 2 weeks (Q2W) for up to 20 doses (~40 weeks) with pembrolizumab monotherapy 200 mg IV infusion every 6 weeks (Q6W) for up to 7 cycles (~42 weeks).
  • Active Comparator: Pembrolizumab
    Participants will receive pembrolizumab 200 mg intravenous (IV) infusion Q3W for up to 12 weeks + double-platinum chemotherapy per neoplasm histology classification at the investigator's discretion as neoadjuvant therapy prior to surgery; followed by pembrolizumab monotherapy 200 mg IV infusion Q6W for up to 7 cycles (~42 weeks).

Geprüfte Regime

  • Sacituzumab tirumotecan (MK-2870):
    Sacituzumab tirumotecan to be administered as 4mg/kg IV infusion q2w for up to 40 weeks
  • Pembrolizumab (MK-3475):
    Pembrolizumab to be administered 400mg by IV infusion q6w for up to 42 weeks
  • Cisplatin:
    Cisplatin is administered as 75 mg/m2 IV infusion q3w for up to 12 weeks as background treatment in neoadjuvant phase
  • Pemetrexed:
    Pemetrexed will be administered in the neoadjuvant phase as 500 mg/m2 IV infusion q3w for up to 12 weeks as background treatment in participants with nonsquamous NSCLC.
  • Gemcitabine:
    Gemcitabine will be administered in the neoadjuvant phase as 1000 mg/m2 or 1250 mg/m2 IV infusion on day 1 and day 8 q3w for up to 24 weeks as background treatment in participants with squamous NSCLC.
  • Carboplatin:
    Carboplatin will be administered in the neoadjuvant phase as AUC 5 mg/mL/min or AUC 6 mg/mL/min IV infusion q3w for up to 12 weeks as background treatment.
  • Paclitaxel:
    Paclitaxel will be administered in the neoadjuvant phase as 175 mg/m2 or 200 mg/m2 IV infusion q3w for up to 12 weeks as background treatment.

Quelle: ClinicalTrials.gov


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