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SNCTP000004212 | NCT03797326 | BASEC2020-02311

Multizentrische, offene Phase-II-Studie zu Lenvatinib (E7080/MK-7902) plus Pembrolizumab (MK-3475) bei vorbehandelten Personen mit ausgewählten soliden Tumoren (LEAP-005)

Data source: BASEC (Imported from 05.03.2021), WHO (Imported from 07.03.2021)
Changed: 07.03.2021
Disease category: Breast Cancer, Colon and Rectal Cancer, Other Cancer

Brief description of trial (Data source: BASEC)

Bei der Kontrolle von Tumoren spielt das Immunsystem eine wichtige Rolle.
Pembrolizumab (MK3475) ist ein Antikörper, der die Hemmung des Immunsystems
durch den Tumor unterbindet respektive beendet und so die körpereigene
Bekämpfung des Tumors steigert.
Lenvatinib ist ein Hemmer eines Moleküls, das in Tumorzellen das Zellwachstum und
die Entstehung neuer Blutgefässe fördert. Durch die Hemmung der
Blutgefässentstehung wird die Nährstoffversorgung des Tumors verringert und somit
das Wachstum des Tumors verlangsamt.
In dieser Studie wird die Wirksamkeit und Sicherheit der Kombination von
Pembrolizumab mit Lenvatinib auf verschiedene Tumorarten untersucht, welche zuvor
schon mit der Standardtherapie/den Standardtherapien behandelt wurden und danach
wieder aufegtreten sind (Rückfall).
Die Studienteilnehmenden erhalten die Studienmedikation für ungefähr 2 Jahre. Nach
Absetzen der Studienmedikation folgt eine Nachbeobachtungsphase.

Health conditions investigated (Data source: BASEC)

Es werden Studienteilnehmer gesucht, die an verschiedenen Arten von soliden Tumoren leiden. Es handelt sich bei diesen Tumoren um eine der folgenden Krebsarten: dreifach-negativer Brustkrebs, Eierstockkrebs, Magenkrebs, Darmkrebs, Glioblastom und Gallengangskarzinom. Alle Teilnehmer haben sich vor der Studie einer oder mehreren erfolglosen Krebsbehandlungen unterzogen und ihr Krebs ist soweit fortgeschritten, dass sich Tumorableger (Metastasen) gebildet haben.

Health conditions (Data source: WHO)

Advanced Solid Tumors;Triple Negative Breast Cancer;Ovarian Cancer;Gastric Cancer;Colorectal Cancer;Glioblastoma;Biliary Tract Cancers;Pancreatic Cancer

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

An der Studie werden weltweit ca. 420 Patienten teilnehmen, ca. 30 davon in der Schweiz.
Nach einer genauen Eignungsabklärung und Eintrittsuntersuchung werden Sie eine Behandlung mit Pembrolizumab plus Lenvatinib erhalten.
Ihr Studienarzt wird dies näher mit Ihnen besprechen.


Behandlungsphase:
Alle Studienteilnehmer erhalten Pembrolizumab (200 mg) als Infusion alle 3 Wochen. Zusätzlich schlucken die Studienteilnehmer täglich eine Tablette Lenvatinib (20 mg). Die Studienbehandlung dauert ca. 2 Jahre, falls sich die Erkrankung in der Zeit nicht verschlechtert; danach kann die Behandlung mit Lenvatinib alleine fortgeführt werden, falls der Patient weiterhin vom Medikament profitiert.
Falls sich die Erkrankung während der Behandlung verschlechtert, wird die Therapie abgebrochen und Ihr Arzt wird mit Ihnen das weitere Vorgehen besprechen.
Im Rahmen der Studientermine können unterschiedliche Massnahmen und Untersuchungen erfolgen:

Gespräche mit dem medizinischen Personal, Blutentnahmen, Blutdruckmessungen, Elektrokardiogramme (EKG), Gewichtsmessung, Urinproben, Scans mit Computertomographen (CT) oder Magnetresonanztomographie (MRT) mit oder ohne intravenös verabreichtem Kontrastmittel, usw.

Nach abgeschlossener Behandlung oder nach Studienabbruch erfolgt nach 30 Tagen eine Nachuntersuchung bevor der Studienteilnehmer in die Nachbeobachtungsphase übertritt.

Nachbeobachtungsphase:
Wurde die Medikation abgesetzt, weil die Behandlungsdauer von 2 Jahren erreicht wurde oder wurde die Medikation aus anderen Gründen als aufgrund des Fortschreitens der Krankheit abgebrochen, wird der Teilnehmer im Rahmen der Nachbeobachtung weiterhin alle 9 Wochen körperlich untersucht.

Wurde die Studienmedikation aufgrund von Fortschreiten der Krankheit oder aufgrund der Notwendigkeit einer neuen Therapie abgebrochen, wird der Studienteilnehmer im Rahmen der Nachbeobachtung alle 12 Wochen kontaktiert und zu seinem Gesndheitszustand befragt.

Interventions (Data source: WHO)

Biological: Pembrolizumab;Drug: Lenvatinib

Criteria for participation in trial (Data source: BASEC)

• Patienten mit einer der folgenden metastasierten Krebsarten: dreifach-negativer Brustkrebs, Eierstockkrebs, Magenkrebs, Darmkrebs, Glioblastom, Gallengangskarzinom (histologisch oder zytologisch bestätigt)

• Der Krebs muss schon mit der Standardtherapie/den Standardtherapien behandelt worden sein und danach wieder aufgetreten sein oder sich verschlechtert haben

•Frisches oder archiviertes Tumorgewebe steht zur Verfügung und es gibt messbare Läsionen

Exclusion criteria (Data source: BASEC)

• Vorhandene Magen-Darm-Erkrankung, welche die Aufnahme von Lenvatinib behindern könnte.

• Flüssigkeitsansammlung im Herzbeutel, Brustraum oder Bauchraum, welche bis 2 Wochen vor Behandlung eine Drainage oder die Einnahme von entwässernden Medikamenten erfodert.

• Patienten mit massgeblicher Herz-Kreislauf Beeinträchtigung innerhalb der
letzten 12 Monaten vor Verabreichung der ersten Dosis der Studienmedikation.

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

- Has a histologically or cytologically-documented, advanced (metastatic and/or
unresectable) solid tumor that is incurable and for which prior standard systemic
therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric
Cancer, Colorectal Cancer, GBM, BTC (intrahepatic, extrahepatic cholangiocarcinoma and
gall bladder cancer; excludes Ampulla of Vater), Pancreatic Cancer

- Must have progressed on or since the last treatment

- Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the
local site investigator/radiology and confirmed by BICR

- Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or
excisional biopsy of a tumor lesion not previously irradiated

- Male participants agree to use approved contraception during the treatment period for
at least 7 days after the last dose of lenvatinib, or refrain from heterosexual
intercourse during this period

- Female participants are not pregnant or breastfeeding, and are not a woman of
childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during
the treatment period (or 14 days prior to the initiation of study treatment for oral
contraception) and for at least 120 days post pembrolizumab, or 30 days post
lenvatinib, whichever occurs last

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3
days of study treatment initiation

- Has adequate organ function

For Triple Negative Breast Cancer Participants:

- Has received one or 2 prior lines of therapy

- Has Lactate Dehydrogenase (LDH) <2.0 x Upper Limit of Normal (ULN)

- Has locally determined results for estrogen receptor, progesterone receptor, and human
epidermal growth factor receptor 2 tumor analyses

For Ovarian Cancer Participants:

- Has received 3 prior lines of therapy. Note: The initial 30 participants in this cohort
included participants with primary ovarian cancer. The expanded cohort will include
participants with primary ovarian cancer, fallopian tube, and peritoneal ovarian cancer.

For Gastric Cancer Participants:

- Has received 2 prior lines of therapy. Note: Gastric cancer will include participants
with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with
squamous cell carcinoma histology are not eligible

For Colorectal Cancer Participants:

- Has received 2 prior lines of therapy

For GBM Participants:

- Has failed initial systemic therapy for newly diagnosed GBM

- Have the following time periods elapsed before the projected start of scheduled study
treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from
stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at
least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent,
5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at
least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies
and 1 week for cancer vaccines

- Be neurologically stable (e.g. without a progression of neurologic symptoms or
requiring escalating doses of systemic steroid therapy within last 2 weeks) and
clinically stable

- Has histologically confirmed World Health Organization (WHO) Grade IV GBM

- Has locally determined result for O^6-methylguanine-DNA methyltransferase (MGMT)
analysis

For Biliary Tract Cancer Participants:

- Has received 1 prior line of therapy

- Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6

For Pancreatic Cancer Participants:

- Has pathologically (histologically or cytologically) confirmed pancreatic ductal
adenocarcinoma that is metastatic at enrollment

- Has received one or 2 prior lines of therapy

- Has received prior therapy with at least 1 (platinum-containing regimen or
gemcitabine-containing regimen) but no more than 2 prior systemic therapies for
unresectable or metastatic pancreatic cancer

Exclusion Criteria:

- Has presence of gastrointestinal condition including malabsorption that might affect
the absorption of lenvatinib

- Has present or progressive accumulation of pleural, ascitic, or pericardial fluid
requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to
all cohorts except the ovarian cancer cohort)

- Has radiographic evidence of major blood vessel invasion/infiltration. Participants
with portal vein invasion (Vp4), inferior vena cava, or cardiac involvement based on
imaging in the BTC cohort are excluded

- Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the
first dose of study treatment

- Has significant cardiovascular impairment within 12 months of the first dose of study
treatment: such as history of congestive heart failure greater than New York Heart
Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular
accident (CVA), or cardiac arrhythmia associated with hemodynamic instability

- Has a history of arterial thromboembolism within 12 months of start of study treatment

- Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.

- Serious nonhealing wound, ulcer or bone fracture

- Has had major surgery within 3 weeks prior to first dose of study interventions

- Has biologic response modifiers (e.g. granulocyte colony-stimulating factor) within 4
weeks before study entry

- Has preexisting =Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula

- Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2
agent or with an agent directed to another stimulatory or co-inhibitory T-cell
receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis
factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor
superfamily member 9 [CD137])

- Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to study treatment start

- If participant received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting study treatment

- Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from al

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03797326

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03797326

Further information on trial

Date trial registered

07.01.2019

Incorporation of the first participant

12.02.2019

Recruitment status

Recruiting

Academic title (Data source: WHO)

A Multicenter, Open-label Phase 2 Study of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) in Previously Treated Subjects With Selected Solid Tumors (LEAP-005)

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Glioblastoma (GBM) by Investigator Assessment in Initial Cohorts;ORR per RECIST 1.1 or RANO (GBM) by Blinded Independent Central Review (BICR) in Expanded Cohorts (Combined with Initial Cohorts);Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Experience an Adverse Event (AE);Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Discontinue Study Treatment Due to an AE;Percentage of Participants Receiving Lenvatinib Monotherapy who Experience an AE;Percentage of Participants Receiving Lenvatinib Monotherapy who Discontinue Study Treatment Due to an Adverse Event (AE)

Secundary end point (Data source: WHO)

Plasma Concentration of Lenvatinib;OS in Lenvatinib Monotherapy Arm;PFS per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm;DOR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm;DCR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm;ORR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm;OS in Expanded Cohorts (Combined with Initial Cohorts);PFS per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts);DOR per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts);DCR per RECIST 1.1 by BICR in Expanded Cohorts (Combined with Initial Cohorts);Overall Survival (OS) in Initial Cohorts;Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts;Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts;Disease Control Rate (DCR) per RECIST 1.1 by Investigator Assessment in Initial Cohorts

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Bellinzona, Bern, Chur, Geneva, St. Gallen, Zurich

Countries (Data source: WHO)

Switzerland might not appear as site of trial if it has not yet been entered as such in the WHO primary registry.
Australia, Canada, Chile, France, Germany, Israel, Korea, Republic of, Spain, United Kingdom, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Klaudia Georgi
+41 586183388
klaudia.georgi@msd.com

Contact for general information (Data source: WHO)

Medical Director;Toll Free Number
Merck Sharp & Dohme Corp.
1-888-577-8839
Trialsites@merck.com

Contact for scientific information (Data source: WHO)

Medical Director;Toll Free Number
Merck Sharp & Dohme Corp.
1-888-577-8839
Trialsites@merck.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Merck Sharp & Dohme Corp.

Additional sponsors (Data source: WHO)

Eisai Inc.

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

12.01.2021

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2020-02311

Secondary ID (Data source: WHO)

2018-003747-37
MK-7902-005
E7080-G000-224
LEAP-005
7902-005