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A Phase 1/2 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - MK-1308-001

Studio Clinico

Patologia: Melanoma, Neoplasie del polmone, Altre neoplasie

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Non applicabile

Criteri di inclusione: 

For Dose Escalation Phase:
- Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit

For Dose Confirmation Phase NSCLC Arms (A, B, C, and E):
- Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. Participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies ≥6 months before dosing of study drug if prior systemic treatment was given for early stage disease

For Dose Confirmation Phase SCLC Arm (Arm D):
- Have histologically - or cytologically - confirmed metastatic (Stage III/IV) SCLC with progressive disease after ≥1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible
- Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
- Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1
- A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies:
 - Is not a woman of child bearing potential (WOCBP) OR
- Is a WOCBP and using a contraceptive method that is highly effective during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, whichever comes last
- Female participants of childbearing potential must have negative urine or serum pregnancy test within 24 hours for urine and within 72 hours for serum prior to receiving the first dose of study treatment
- Male participants with a female partner(s) of child-bearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication and refrain from donating sperm during this period
- Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample)

For Efficacy Expansion Phase Arms F and G and Coformulation Phase Arm J:
- Have histologically/cytologically-confirmed unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy
- Have at least 1 measurable lesion by CT or MRI per RECIST 1.1. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions
- Participants with unresectable Stage III or IV disease must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (combinations with anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4] agents will not be allowed)
- Participants who receive anti-PD-1 therapy as adjuvant treatment following complete resection of Stage III or IV melanoma and have disease recurrence (unresectable loco-regional disease or distant metastases) while on active treatment or within 6 months of stopping anti-PD-1 are eligible
- Have submitted pre-trial imaging and provided a baseline tumor sample
- Proto-oncogene B-raf (BRAF) V600 mutation-positive melanoma participants should have received targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, they are not required to progress on this treatment prior to enrollment
- BRAF V600E mutation-positive melanoma participants who have NOT received a BRAF inhibitor (either as adjuvant therapy or in the metastatic disease setting) with lactate dehydrogenase (LDH) < local upper limit of normal (ULN), no clinically significant tumor-related symptoms, and absence of rapidly progressing metastatic melanoma. Approximately 10 participants each from Arms F, G, and J will have 2 mandatory biopsies

For Dose Coformulation Phase Arm I:
- Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for or refused all treatment known to confer clinical benefit
- Meet all requirements for Dose Escalation Phase and Dose Confirmation Phase.

Criteri di esclusione: 

For all phases of the study:
- Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4
For Dose Confirmation Phase:
- Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment
- Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years

For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E):
- Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis
- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE)
- Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug
- Has any active infection requiring therapy
- Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has clinically significant cardiac disease
- Has received a live-virus vaccine within 28 days of planned treatment start
- Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA
- Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab, or up to 180 days after the last dose of chemotherapeutic agents, whichever comes last
- Has not fully recovered from any effects of major surgery without significant detectable infection

For Arm F and G (Efficacy Expansion Phase) and Arm J (Coformulation Phase) ONLY:
- Has known active CNS metastases and/or carcinomatous meningitis
- Has not had resolution of anti-PD-1 antibody-related AEs, including immune-mediated AEs back to Grade ≤1 or baseline
- Has not discontinued steroid treatment for an irAE for at least 2 weeks prior to the first dose of study drug
- Has ocular melanoma
- Has mucosal melanoma
- Has had an allogenic tissue/solid organ transplant.

Trattamento sperimentale: 

- Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1
- Escalation: DL 2 Quavonlimab + Pembro: Cohort 2
- Escalation: DL 3 Quavonlimab + Pembro: Cohort 3
- Confirmation: DL 1 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm A
- Confirmation: DL 1 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm B
- Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm C
- Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (SCLC): Arm D
- Confirmation: DL 2 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm E
- Expansion: DL1 Quavonlimab Schedule 2 + PDL2 Pembro Schedule 2: Arm F
- Expansion: DL1 Quavonlimab Schedule 2 Monotherapy: Arm G
- Coformulation: Pembrolizumab/Quavonlimab Schedule 2: Arm I
- Coformulation Phase: Pembrolizumab/Quavonlimab Schedule 2: Arm J

Trattamento di controllo: 


Centri partecipanti

Nord Italia

Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD


Centro Italia

Azienda Ospedaliera Universitaria Senese
Viale Bracci 16 - 53100 Siena - SI
Policlinico Le Scotte


Sud Italia e isole

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA

Riferimento: Dr. Paolo Ascierto
Telefono: 0815903236

Informazioni Generali


Numero di iscrizione a registro: 2019-003703-35

Data di inserimento: 03.08.2021


Merck Sharp & Dohme Corp.

Principal Investigator ITALIA

Istituto Nazionale Tumori IRCCS 'Fondazione Pascale', Napoli

Riferimento: Dr. Paolo Ascierto

Telefono: 0815903236


Localita: Napoli


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