Phase II, open label, single arm study of PembrolizumAb combiNeD with cisplatin or carbOplatin and etoposide in treatment naïve advanced meRkel cell cArcinoma (MCC) (PANDORA Trial).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori, Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

18 Dec 2023 → ongoing

Decision date (initial)

2023-10-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

MERCK SHARP & DOHME CORP.

External identifiers

EU CT number

2022-500988-12-00

WHO UTN

U0000-0000-0000

ClinicalTrials.gov

NCT00000000

ISRCTN

ISRCTN00000000

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC

Secondary objectives 1

1. To assess safety and efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC

Conditions and MedDRA coding

Advanced, naïve, Merkel cell carcinomas

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Patients must be capable of giving signed informed consent
2. Ability to comply with protocol requirements
3. Patients must be ≥18 years of age at the time of signing the ICF
4. Locally advanced, relapsed or metastatic MCC stage IIIB-IV according to American Joint Committee on Cancer (AJCC) TNM Staging Classification for Merkel Cell Carcinoma (8th ed. 2017)
5. Histologically confirmed diagnosis of MCC.
6. Availability of tumor sample (obtained from core biopsy or surgical specimen) is mandatory for PD L1 expression assessment and biomolecular characterization.
7. Life expectancy ≥ 3 months
8. Measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
10. No previous systemic therapy for advanced disease
11. Patients with treated or asymptomatic brain metastases may be enrolled
12. Women of childbearing potential must use 2 effective methods of contraception with a failure rate of less than 1% per year, during the entire study treatment period and for a period of 5 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and us usual lifestyle of the subject. They must have a negative serum pregnancy test during the screening period.
13. Adequate haematological function defined by white blood cell (WBC) count ≥2,500/mm 3 with absolute neutrophil count (ANC) ≥1,500/mm 3, platelet count ≥ 100,000/mm 3 and haemoglobin ≥9 g/dL
14. Adequate hepatic function defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN) range (except subjects with Gilbert Syndrome), serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 if liver function test elevations are due to liver metastases)
15. Adequate renal function defined by a serum creatinine ≤ 1.5 x ULN or an estimated creatinine clearance of ≥ 30 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft Gault formula)
16. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria

Exclusion criteria 20

1. Prior treatment with pembrolizumab or any other immunotherapy agents (anti PD 1, anti PD L1, anti PD L2, anti CD137, anti CTLA 4 antibodies, or any other antibody or drug specifically targeting T cell costimulatory immune checkpoint pathways)
2. Other concurrent neoplasms requiring active treatment
3. Prior organ transplantation, including allogenic stem cell transplantation
4. Any medical condition, within 6 months before receiving the first dose of study drug, considered relevant by Investigator.
5. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
6. Serious infection within 14 days before the first dose of study drug
7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
8. Active tuberculosis
9. Pregnancy or breastfeeding
10. Vaccination within 4 weeks of the first dose and while on trial is prohibited except for administration of inactivated vaccines
11. Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel
12. Prior treatment with chemotherapy for advanced MCC with the exception for subjects who received adjuvant or neoadjuvant therapy. They are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the onset of metastatic disease.
13. Known hypersensitivity to pembrolizumab, carboplatin, cisplatin and/or etoposide
14. Concurrent anticancer treatment, immune therapy, or cytokine therapy, except for erythropoietin
15. Major surgery for any reason within 4 weeks from registration and/or if the subject has not fully recovery from the surgery within 4 weeks of treatment start
16. Subjects receiving immunosuppressive agents such as steroids for any reason should be tapered of these drugs before initiation of the trial treatment. Low dose corticosteroid therapy will be allowed.
17. Known severe hypersensitivity reactions to chimeric or monoclonal antibodies, fusion proteins
18. Patients with untreated, symptomatic and/or progressive brain metastases, or with carcinomatous meningitis. Subjects with brain metastases are eligible if metastases have been treated and there is no clinical evidence of progression
19. History of active autoimmune diseases. Subjects with diabetes mellitus type I, hypothyroidism only requiring hormone replacement or controlled hyperthyroidism, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
20. Adjuvant radiotherapy is permitted if ended ≥ 6 months before trial enrollment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR, that will be defined as the percentage of patients achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria

Secondary endpoints 6

1. Incidence of Serius Adverse Events (SAE)
2. Incidence and severity of Immune-mediated Adverse Events (imAE)
3. Incidence and severity of Adverse Events (AEs) according to NCI Common Terminology criteria Adverse Event (CTCAE), version 5.0
4. Overall Survival (OS) that will be measured from the date of starting therapy to the date of death by any cause
5. Progression Free Survival (PFS) that will be measured from the date of starting therapy to the date of disease progression or death.
6. Duration of Response (DOR) that will be measured from the date of the first response to disease progression or death in those patients who achieved a CR o PR during study treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Clinical trial contact point

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Clinical trial contact point

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications