Patologia: Neoplasie del polmone
Fase di studio: II Randomizzato
Richiesta mandatoria di tessuto: Sì
Linee di trattamento: Seconda linea, Terza/N linea
Criteri di inclusione:
1.Has a histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV: M1a, M1b, M1c, AJCC Staging Manual, version 8). Note: Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible.
2.Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of the absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], AND absence of ALK and ROS1 gene rearrangements).
Note: If participant’s tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK and ROS1 translocations will not be required, as this is not part of current diagnostic guidelines.
3.Has PD on treatment with one prior anti-PD-1/PD-L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. Anti-PD-1/PD-L1 treatment progression is defined by meeting ALL of the following criteria:
-Treatment with at least 2 doses of an anti-PD-1/PD-L1 mAb.
-PD after an anti-PD-1/PD-L1 mAb as defined by RECIST 1.1, based on the following:
-imaging before anti-PD-1/PD-L1 treatment or image showing nadir during anti-PD-1/PD-L1 treatment; AND
-imaging to determine that radiographic progression has occurred per RECIST 1.1 within 12 weeks (84 days) from the last dose of an anti-PD-1/PD-L1 mAb.
Note: Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment.
4. Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease.
Note: A platinum-containing doublet is defined as a platinum-based cytotoxic systemic agent administered in the same cycle as another cytotoxic systemic chemotherapeutic agent.
Note: Completion of treatment with a platinum-containing doublet as neo-adjuvant or adjuvant therapy or as part of definitive chemo-radiation treatment for early stage disease.
5.Has measurable disease based on RECIST 1.1, as determined by the local site assessment.
Note: Measurable disease is defined as having at least 1 measurable lesion by CT or MRI per RECIST 1.1. Lesions that appear measurable, but are situated in a previously irradiated area can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
6.Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample
(defined as: from initial diagnosis of NSCLC and before receiving immunotherapy [anti-PD-1/PD-L1], from the primary lesion or a metastatic lesion) or newly obtained (defined as: after completion of immunotherapy [anti-PD-1/PD-L1] and before receiving a randomization number) core or excisional biopsy of a tumor lesion not previously irradiated.
7.Is male or female, ≥18 years of age at the time of providing documented informed consent.
8.Has a life expectancy of at least 3 months.
9.Has an ECOG Performance Status of 0 to 1 assessed within 7 days prior to randomization.
Note: The tissue sample must be received and evaluated by the central vendor before randomization for stratification in the study. FFPE tissue blocks are preferred to slides. Details pertaining to tumor tissue submission can be found in the Procedures Manual.
10.Male participants randomized to docetaxel are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of docetaxel:
-Refrain from donating sperm
-Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-
term and persistent basis) and agree to remain abstinent.
-Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause [Appendix 5]) as detailed below:
Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
11. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
-Is not a WOCBP
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 5 during the intervention period and for at least 120 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
-A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention.
-A WOCBP randomized to docetaxel is eligible to participate if she is using a contraceptive method that is highly effective with low user dependency or is abstinent from heterosexual intercourse as her preferred and usual lifestyle and agrees not to donate or freeze/store eggs during the intervention period and for at least 180 days after the last dose of docetaxel.
-If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
-Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.5.
-The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
-Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirement above, the local label requirements are to be followed.
12.The participant (or legally acceptable representative if applicable) provides written: informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
13. Has adequate organ function as defined in Table 3. Specimens must be collected within 10 days before the start of study intervention.
Criteri di esclusione:
Numero di pazienti previsti:
Schema di trattamento:
MK7684A vs MK7684A+Docetaxel vs Placebo+MK7684A
MK7684A monotherapy & MK7684A plus Docetaxel
Trattamento di controllo:
Placebo plus Docetaxel
Obiettivi primari dello studio:
Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment [Time Frame: Up to approximately 27 months]
Obiettivi secondari dello studio:
1.Objective Response (OR) per RECIST 1.1 by BICR Assessmen
2. Overall Survival
3. Duration of Response by BICR assessment
4. Number of participants who experienced an AE
5.Number of partipants who dIscontinued Study Treatment due to an AE
Data di inizio dell'arruolamento: 30.03.2021
Data di fine dell'arruolamento: 12.08.2022
Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI
Riferimento: Prof. Filippo De Marinis
Ospedale San Raffaele di Milano
Via Olgettina 60 - 20132 Milano - MI
Centro di Riferimento Oncologico
Via Franco Gallini 2 - 33081 Aviano - PN
Riferimento: Dr.ssa Elisa De Carlo
A.O.U San Luigi Gonzaga
Regione Gonzole 10 - 10043 Orbassano - TO
Riferimento: Prof.ssa Silvia Novello
Largo Brambilla 3 - 50134 Firenze - FI
Riferimento: Prof. Lorenzo Antonuzzo
Azienda Ospedaliera S. Giovanni Addolorata Roma
Via Dell’Amba Aradam 9 - 00184 Roma - RM
Fondazione Policlinico A. Gemelli
Largo Agostino Gemelli 8 - 00168 Roma - RM
Riferimento: Prof. Emilio Bria
Azienda Ospedaliera Vincenzo Monaldi
Via Leonardo Bianchi 1 - 80131 Napoli - NA
Numero di iscrizione a registro: 2020-004034-38
Data di inserimento: 10.05.2022
Merck Sharp & Dohme LLC
Istituto Europeo di Oncologia - IEO
Riferimento: Prof. Filippo De Marinis