Clinical trial of combined therapy with pembrolizumab and lenvatinib for patients with classic Kaposi sarcoma treated with at least one previous line of chemioterapy.

2024-512834-14-00 Protocol MK-3475-B60 Therapeutic exploratory (Phase II) Ended

End 15 Oct 2025 · Status Ended · 1 EU/EEA countries · 1 sites · Protocol MK-3475-B60

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ended
Participants planned 25
Countries 1
Sites 1

Advanced unresectable classic Kaposi sarcoma relapsed and/or refractory to previous standard treatments.

The main objective of the study is to evaluate the response rate to the treatment with pembrolizumab and lenvatinib in patients with previously treated relapsed/refractory Kaposi sarcoma.

Key facts

Sponsor
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
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
completed 15 Oct 2025
Decision date (initial)
2024-12-02
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
Merck Sharp & Dohme Corp. Italia

External identifiers

EU CT number
2024-512834-14-00
EudraCT number
2020-004426-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Others, Efficacy

The main objective of the study is to evaluate the response rate to the treatment with pembrolizumab and lenvatinib in patients with previously treated relapsed/refractory Kaposi sarcoma.

Secondary objectives 3

  1. the evaluation of the duration of response;
  2. evaluation of the impact of combination therapy on survival
  3. treatment tolerability in this patients’ subgroup (including evaluation of the incidence of treatment related adverse events, and the impact of treatment on the patients’ quality of life).

Conditions and MedDRA coding

Advanced unresectable classic Kaposi sarcoma relapsed and/or refractory to previous standard treatments.

VersionLevelCodeTermSystem organ class
20.0 PT 10023284 Kaposi's sarcoma 100000004864

Study design 3 periods

#TitleAllocationBlindingRoles blindedArms
1 Screening
A screening examination should be performed between 1 and 28 days before- treatment. During the screening phase the activities performed will be: - Informed Consent sign - Demographics and Medical History - Prior/Concomitant Medication Review - Tumor imaging and response assessment - Dermatological evaluation (+ target lesion photographs) - Safety Laboratory Assessments -Evaluation of Inclusion and Esclusion criteria Subjects who fulfill all the inclusion and none of the exclusion criteria will be accepted into the study.
 Not Applicable None single-arm: Single arm: Pembrolizumab + Lenvatinib treatment
2 Treatment period
Treatment period will start after all screening procedures are completed. Participants will receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (approximately 2 years) plus lenvatinib 20 mg via oral capsule daily for up to 2 years.Tumor response will be evaluated according to clinical criteria (dermatological examination) and per RECIST 1.1, when feasible. Dermatological assessments for disease response will be performed at baseline, at Cycle 2 Day 1, and every even cycle thereafter. Radiological disease assessment will be performed at baseline and every 6 months until disease progression. Participants who have been on pembrolizumab for at least 24 weeks and attain a CR may consider stopping pembrolizumab treatment. These participants, as well as those who stop pembrolizumab treatment after receiving 35 administrations of pembrolizumab may be eligible for up to 17 additional administrations of pembrolizumab ±lenvatinib (approximately 1 year) in the Second-Course Treatment Phase upon experiencing PD.
 Not Applicable None single-arm: Single arm: Pembrolizumab + Lenvatinib treatment
3 Follow-up period
After treatment discontinuation or treatment completation, patients will enter a follow up period: all subjects will be followed for progression free survival (PFS), OS and late-onset adverse events (AEs). Assessment of survival status will be performed approximately every 3 months.
 Not Applicable None single-arm: Single arm: Pembrolizumab + Lenvatinib treatment

Regulatory references

Plan to share IPD
Yes
IPD plan description
The shared data will be all of the individual participant data collected during the trial, after deidentification.
EU CT numberTitleSponsor
2023-506987-15-00 Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-365) Merck Sharp & Dohme LLC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Histologic diagnosis of classic Kaposi sarcoma;
  2. progression, relapse or inadequate response to at least one prior systemic chemotherapy;
  3. presence of measurable disease by Positron Emission Tomography-Computed Tomography (PET-CT) scan and/or dermatological examination;
  4. at least 1 superficial lesion willing to provide tissue from cutaneous and/or mucosal biopsy at baseline;
  5. be = 18 years of age at the time of signing informed consent;
  6. have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 within 7 days before the first dose of study intervention;
  7. have adequate bone marrow, liver and renal function;
  8. have adequately controlled blood pressure.

Exclusion criteria 7

  1. Has a known history of human immunodeficiency virus (HIV) infection, of active infectious hepatitis type B (hepatitis B surface antigen [HBsAg] detected) or C (hepatitis C virus [HCV] ribonucleic acid [RNA] detected) or active Tuberculosis Bacillus (TB);
  2. presence of known additional malignancy that is progressing or requires active treatment;
  3. has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs);
  4. has had an allogeneic tissue/solid organ transplant;
  5. significant cardiovascular impairment within 12 months of the first dose of study intervention;
  6. history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption;
  7. previous immunotherapy with ICI(s).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary endpoint of the study is to estimate the overall response rate (ORR) during treatment with pembrolizumab and lenvatinib in patients with previously treated relapsed/refractory classic Kaposi sarcoma.

Secondary endpoints 8

  1. To estimate the duration of response (DOR) in patients with pre-treated recurrent CKS receiving pembrolizumab with lenvatinib
  2. to estimate the progression free survival (PFS);
  3. to estimate the overall survival (OS);
  4. to estimate the mean change from baseline in the global health status/quality of life (QoL), and physical functioning for the combinations of pembrolizumab and lenvatinib;
  5. to estimate the safety and tolerability for the combination of pembrolizumab and lenvatinib
  6. to evaluate changes in plasma levels of HHV8 DNA at baseline and at the time of treatment discontinuation, due to any cause (i.e. disease progression, complete response, unacceptable treatment related toxicity)
  7. to evaluate changes in plasma levels of circulating markers (i.e. PD-1/PD-L1, VEGF, VEGF-R) at baseline and at the time of treatment discontinuation, due to any cause (i.e. disease progression, complete response, unacceptable treatment related toxicity)
  8. to analyze PD-L1 and VEGF expression, and tumor infiltrating lymphocytes in tumor specimens at baseline and at the time of disease progression (optional)

Investigational products

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

Test 3

Lenvatinib

PRD9414230 · Product

Active substance
Lenvatinib
Pharmaceutical form
CAPSULE
Route of administration
ORAL
Max daily dose
20 mg milligram(s)
Max total dose
20 d day
Max treatment duration
24 Month(s)
Authorisation status
Not Authorised
MA holder
MERCK & CO. INC.
Paediatric formulation
No
Orphan designation
No

Lenvatinib

PRD9414231 · Product

Active substance
Lenvatinib
Pharmaceutical form
CAPSULE
Route of administration
ORAL
Max daily dose
20 mg milligram(s)
Max total dose
20 d day
Max treatment duration
24 Month(s)
Authorisation status
Not Authorised
MA holder
MERCK & CO. INC.
Paediatric formulation
No
Orphan designation
No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323105 · Product

Active substance
Pembrolizumab
Substance synonyms
Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
200 mg milligram(s)
Max total dose
200 d day
Max treatment duration
24 Month(s)
Authorisation status
Authorised
ATC code
L01FF02 — -
Marketing authorisation
EU/1/15/1024/002
MA holder
MERCK SHARP & DOHME B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

3 Total trials 3 Ended
Academic / Non-commercial
Sponsor organisation
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Address
Via Francesco Sforza 28
City
Milan
Postcode
20122
Country
Italy

Scientific contact point

Organisation
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Contact name
Ornella Garrone

Public contact point

Organisation
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Contact name
Ornella Garrone

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Ended 25 1
Rest of world — 0 —

Investigational sites

Italy

1 site · Ended
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Area Medica - Oncologia Medica, Via Francesco Sforza 28, 20122, Milan

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) 2024-512834-14_D1_Protocol_IT_v1-4_20Dec2023_Eng-FOR PUB 1.4
Recruitment arrangements (for publication) K1_Recruitment_Blank document_04Oct2024_IT_Eng NA
Subject information and informed consent form (for publication) 2024-512834-14_L1_CEC Approval Initial_IT_22Mar2021_Ita-FOR PUB redacted NA
Subject information and informed consent form (for publication) 2024-512834-14_L1_CEC SA1_IT_28Oct2022_Ita-FOR PUB-redacted NA
Subject information and informed consent form (for publication) 2024-512834-14_L1_CET SA3_IT_03Apr2024_Ita-FOR PUB redacted NA
Subject information and informed consent form (for publication) 2024-512834-14_L1_SIS-ICF Main_IT_v1-7_20Dec2023_Ita 1.7
Subject information and informed consent form (for publication) 2024-512834-14_L1_SIS-ICF Personal Data_IT_v1-2_18Jun2022_Ita 1.2
Subject information and informed consent form (for publication) 2024-512834-14_L1_SIS-ICF Supplementar procedures_IT_v1-3_18Jun2022_Ita 1.3
Synopsis of the protocol (for publication) 2024-512834-14_D1_Protocol Synopsis_IT_v1-3_20Dec2023_Ita 1.3

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-10 Italy Acceptable
2024-11-25
 2024-12-02

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