Donnerstag, 24. Juni 2021
Navigation öffnen
Anzeige:
Kisqali
Kisqali
 
JOURNAL ONKOLOGIE – STUDIE

A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and Cemiplimab in Patients With Advanced Solid Tumors

Rekrutierend

NCT-Nummer:
NCT03192345

Studienbeginn:
Juni 2017

Letztes Update:
09.02.2021

Wirkstoff:
SAR439459, Cemiplimab REGN2810

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Sanofi

Collaborator:
-

Studienleiter

Clinical Sciences & Operations
Study Director
Sanofi

Kontakt

Trial Transparency email recommended (Toll free number for US & Canada)
Kontakt:
Phone: 800-633-1610
Phone (ext.): 1 then #
E-Mail: Contact-Us@sanofi.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 41)

Investigational Site Number 2760001
45122 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Investigational Site Number 2760003
30625 Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Investigational Site Number 8400007
91010 Duarte
United StatesRekrutierend» Google-Maps
Investigational Site Number 8400004
66205 Fairway
United StatesRekrutierend» Google-Maps
Investigational Site Number 8400001
02114 Boston
United StatesRekrutierend» Google-Maps
Investigational Site Number 8400101
02115 Boston
United StatesRekrutierend» Google-Maps
Investigational Site Number 8400008
27710 Durham
United StatesRekrutierend» Google-Maps
Investigational Site Number 8400006
37203 Nashville
United StatesRekrutierend» Google-Maps
Investigational Site Number 8400003
75230 Dallas
United StatesAbgeschlossen» Google-Maps
Investigational Site Number 0360002
3081 Heidelberg West
AustraliaRekrutierend» Google-Maps
Investigational Site Number 0360001
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Investigational Site Number 0560002
1200 Bruxelles
BelgiumRekrutierend» Google-Maps
Investigational Site Number 0560001
3000 Leuven
BelgiumRekrutierend» Google-Maps
Investigational Site Number 1240003
T2N 4N2 Calgary
CanadaRekrutierend» Google-Maps
Investigational Site Number 1240002
H3T 1E2 Montreal
CanadaRekrutierend» Google-Maps
Investigational Site Number 1240001
M5G 2M9 Toronto
CanadaRekrutierend» Google-Maps
Investigational Site Number 2330001
13419 Tallinn
EstoniaRekrutierend» Google-Maps
Investigational Site Number 2500006
59037 Lille
FranceRekrutierend» Google-Maps
Investigational Site Number 2500002
13385 Marseille
FranceRekrutierend» Google-Maps
Investigational Site Number 2500003
44093 Nantes
FranceRekrutierend» Google-Maps
Investigational Site Number 2500005
44093 Nantes
FranceRekrutierend» Google-Maps
Investigational Site Number 2500004
75010 Paris
FranceRekrutierend» Google-Maps
Investigational Site Number 2500001
94805 Villejuif
FranceRekrutierend» Google-Maps
Investigational Site Number 3800001
20133 Milano
ItalyRekrutierend» Google-Maps
Investigational Site Number 3800002
20141 Milano
ItalyRekrutierend» Google-Maps
Investigational Site Number 3800003
20089 Rozzano
ItalyRekrutierend» Google-Maps
Investigational Site Number 4100001
03080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Investigational Site Number 4100002
138-736 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Investigational Site Number 5280001
3015 GD Rotterdam
NetherlandsRekrutierend» Google-Maps
Investigational Site Number 5280002
3584 CX Utrecht
NetherlandsRekrutierend» Google-Maps
Investigational Site Number 7240002
08003 Barcelona
SpainRekrutierend» Google-Maps
Investigational Site Number 7240001
08035 Barcelona
SpainRekrutierend» Google-Maps
Investigational Site Number 7240006
08036 Barcelona
SpainRekrutierend» Google-Maps
Investigational Site Number 7240003
28040 Madrid / Madrid
SpainRekrutierend» Google-Maps
Investigational Site Number 7240004
28050 Madrid / Madrid
SpainRekrutierend» Google-Maps
Investigational Site Number 7240005
31008 Pamplona
SpainRekrutierend» Google-Maps
Investigational Site Number 1580003
807 Kaohsiung
TaiwanRekrutierend» Google-Maps
Investigational Site Number 1580002
704 Tainan
TaiwanRekrutierend» Google-Maps
Investigational Site Number 1580001
Taipei 100
TaiwanRekrutierend» Google-Maps
Investigational Site Number 8260002
CF14 2TL Cardiff
United KingdomRekrutierend» Google-Maps
Investigational Site Number 8260001
G12 0YN Glasgow
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The duration of the study for an individual patient will start from the signature of the main

informed consent and include a screening period of up to 4 weeks (28 days), a treatment

period of at least 1 or 2 cycles (21 or 14 days per cycle, respectively), an end-of-treatment

visit at least 30 days following the last administration of study drug (or until the patient

receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months

after treatment discontinuation and every 3 months following, until disease progression, or

initiation of another antitumor treatment, or death, whichever is earlier. For the urothelial

cancer cohort in Part 2B, follow-up visits will occur every 3 months until death or the

cutoff date for the overall survival analysis (approximately 12 months after last patient

first dose), whichever comes first.

Patients who have no disease progression, and continue to benefit from the study drug(s),

will be allowed to continue treatment beyond the common study end-date at their assigned dose

unless the study is terminated by the Sponsor. The expected enrollment period is

approximately 42 months.

Ein-/Ausschlusskriterien

Inclusion criteria:

Dose escalation (Part 1A and Part 1B)

- Patients with histologically confirmed, advanced unresectable or metastatic solid

tumor whom in the opinion of the Investigator does not have a suitable alternative

therapy.

Dose expansion (Part 2A)

- Patients with histologically confirmed, advanced unresectable or metastatic melanoma

whom in the opinion of the Investigator does not have a suitable alternative therapy.

- Patients must have failed after any prior therapy based on anti-PD-1 or anti-PD-L1 as

defined by disease progression within 26 weeks of initiating anti-PD-1 or anti-PD-L1

based therapy without any evidence of a response (primary resistance to anti-PD-1 or

anti-PD-L1).

- Patients must have a site of disease amenable to biopsy and be a candidate for tumor

biopsy. Patients must be able and willing to provide mandatory tumor biopsies prior to

and during study treatment.

Dose expansion (Part 2B)

- Patients with disease location amenable to mandatory tumor biopsy at baseline with

histologically confirmed advanced unresectable or metastatic melanoma, colorectal

adenocarcinoma, urothelial cancer, hepatocellular carcinoma (HCC), or non-small cell

lung cancer (NSCLC).

- Melanoma patients must have failed one prior therapy based on anti-PD-1 or anti-PD-L1.

- Patients with colorectal cancer must have progressed after last line of therapy.

- Patients with urothelial cancer must have disease progression during or following

platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant

treatment with platinum-containing chemotherapy. Patients must not have received >2

lines of therapy for advanced disease. Patients must not have received prior treatment

with anti-PD-1 or anti-PD-L1.

- Patients with HCC must have failed after 1 prior therapy based on anti-PD-1 or

anti-PD-L1.

- Patients with NSCLC must have failed during or after 1 prior therapy based on

anti-PD-1 or anti-PD-L1.

- Patients with histologically confirmed, advanced unresectable or metastatic melanoma,

or colorectal cancer or NSCLC whom in the opinion of the Investigator do not have a

suitable alternative therapy.

Dose expansion parts 2A and 2B

- At least 1 measurable lesion by RECIST v1.1.

All cohorts

- Patient understands and has signed Informed Consent form and is willing and able to

comply with the requirements of the trial.

Exclusion criteria:

- Age <18 years or < the country's legal age of majority if the legal age is more than

18 years.

- Eastern Cooperative Oncology Group (ECOG) performance status >1.

- Concurrent treatment with any other anticancer therapy (including radiotherapy or

investigational agents) or participation in another clinical study.

- Washout period of less than 3 weeks to prior anticancer therapy.

- Women of reproductive potential and male subjects with female partners of childbearing

potential who are not willing to avoid pregnancy by using highly effective

contraceptive.

- Pregnant or breast-feeding women.

- Unwillingness and inability to comply with scheduled visits, drug administration plan,

laboratory tests, other study procedures, and study restrictions.

- Significant and uncontrolled concomitant illness, including any psychiatric condition.

- Active infections, including unexplained fever (temperature >38.1ºC), or antibiotic

therapy within 1 week prior to enrollment.

- Any prior organ transplant including allogeneic bone marrow transplant.

- History within the last 5 years of an invasive malignancy other than the one treated

in this study, with the exception of resected/ablated basal or squamous-cell carcinoma

of the skin or carcinoma in situ of the cervix, or other local tumors considered cured

by local treatment.

- History of known human immunodeficiency virus (HIV), HIV serology at screening will be

conducted only for patients in German study sites.

- Known uncontrolled hepatitis B virus (HBV) infection.

- Known untreated current hepatitis C virus (HCV) infection.

- Any major surgery within the last 28 days.

- Patients with primary central nervous system (CNS) tumors and/or CNS metastases of

non-CNS primary tumors.

- History of congestive heart failure, myocardial infarction with reduced ejection

fraction, symptomatic coronary artery disease, documented uncontrolled hypertension,

major clinically significant Electrocardiography (ECG) and echocardiogram

abnormalities, significant ventricular arrhythmias, significant valvular heart disease

(including valve replacement), vascular malformation, aneurysm, significant pulmonary

conditions such as idiopathic pulmonary hypertension, uncontrolled chronic lung

disease.

- History of severe, acute or chronic renal diseases.

- Any of the following within 6 months prior to study enrollment: pulmonary embolism,

deep vein thrombosis, active uncontrolled bleeding, infectious or inflammatory bowel

disease, diverticulitis, intestinal obstruction or perforation and gastrointestinal

hemorrhage.

- Inadequate hematological, renal or liver function.

- Non-resolution of any prior treatment related toxicity to Grade <2.

- Prior treatment with any anti-transforming growth factor β (anti-TGFβ) inhibitors.

- Known allergies to any component of SAR439459 and/or cemiplimab.

- Patients with uveal melanoma and patients with prior or ongoing uveitis.

- Patients who received prior immunotherapy who developed toxicity leading to a

permanent discontinuation of immunotherapy.

- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that

required treatment with systemic immunosuppressive treatments.

- Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within

4 weeks prior to the first dose of SAR439459 and/or cemiplimab (occasional use of

inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).

- History of interstitial lung disease or active non-infectious pneumonitis that

required immune-suppressive doses of glucocorticoids to assist with management.

- Patients with underlying cancer predisposition syndromes.

- Receipt of a live vaccine within 30 days of planned start of study medication.

- Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior the

first dose of SAR439459.

- Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × upper limit of

normal (ULN).

- Patients accommodated in an institution because of regulatory or legal order;

prisoners or patients who are legally institutionalized.

The above information is not intended to contain all considerations relevant to a patient's

potential participation in a clinical trial.

Studien-Rationale

Primary outcome:

1. Incidence of Dose Limiting Toxicities (DLTs) (Time Frame - Through the end of 1 or 2 cycles, total duration up to 6 weeks (for Part 1A each cycle is 2 weeks; for Part 1B each cycle is 2 or 3 weeks)):
Incidence of DLTs at Cycle 1 and/or 2 in Parts 1A and 1B.

2. Objective Response Rate (ORR) for Part 2B (Time Frame - Continuous throughout study assessment (up to approximately 1 year)):
Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2B).

Secondary outcome:

1. Overall safety profile (Time Frame - Continuous throughout study assessment (up to approximately 1 year)):
The overall safety profile of SAR439459 administered in monotherapy (Part 1A and Part 2A) or in combination with cemiplimab (Part 1B and Part 2B).

2. Progression free survival (PFS) (Time Frame - Continuous throughout study assessment (up to approximately 1 year)):
The time from first investigational medicinal product (IMP) administration until objective tumor progression or death (Part 2A and Part 2B).

3. Time to progression (TTP) (Time Frame - Continuous throughout study assessment (up to approximately 1 year)):
The time from first IMP administration until objective tumor progression (Part 2A and 2B).

4. Objective Response Rate (ORR) Part 2A (Time Frame - Continuous throughout study assessment (up to approximately 1 year)):
Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2A).

5. Duration of response Part 2B (Time Frame - Continuous throughout study assessment (up to approximately 1 year)):
Time from initial response to the first documented tumor progression.

6. Disease Control Rate Part 2B (Time Frame - Continuous throughout study assessment (up to approximately 1 year)):
Sum of complete response, partial response and stable disease rates

7. Immunogenicity evaluation (Time Frame - Up to approximately 1 year):
Blood samples will be assessed for human anti-SAR439459 antibodies (all cohorts) and for human anti-cemiplimab antibodies (Parts 1B and 2B).

8. Cmax for SAR439459 and for cemiplimab (Time Frame - Cycle 1, Day 1 to Day 15 or to Day 22):
Maximum plasma concentration observed.

9. AUC for SAR439459 (Time Frame - Cycle 1, Day 1 to Day 15 or to Day 22):
Area under the serum concentration versus time curve extrapolated to infinity.

10. AUC0-tau for SAR439459 and for cemiplimab (Time Frame - Cycle 1, Day 1 to Day 15 or to Day 22):
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to 14 or 21 days post-dose.

11. t1/2z for SAR439459 (Time Frame - Cycle 1, Day 1 to Day 15 or to Day 22):
Terminal half-life associated with the terminal slope (λz).

12. CL for SAR439459 (Time Frame - Cycle 1, Day 1 to Day 15 or to Day 22):
Total body clearance of a drug from plasma calculated using the following equation from AUC: CL= Dose/AUC on cycle 1.

13. Vss for SAR439459 (Time Frame - Cycle 1, Day 1 to Day 15 or to Day 22):
Estimate of Volume of distribution at the steady state after single intravenous dose.

Studien-Arme

  • Experimental: Dose Escalation SAR439459 monotherapy
    SAR439459 administered intravenously every 2 weeks in a 14-day cycle with escalating doses
  • Experimental: Dose Expansion SAR439459 monotherapy
    SAR439459 administered intravenously every 3 weeks in a 21-day cycle with the previously determined recommended doses as the patients will be randomized to 2 different doses
  • Experimental: Dose Escalation SAR439459 + cemiplimab combination
    SAR439459 + cemiplimab combination administered intravenously every 2 weeks in a 14-day cycle or every 3 weeks in a 21-day cycle with escalating SAR439459 doses and cemiplimab
  • Experimental: Dose Expansion SAR439459 + cemiplimab combination
    SAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with previously determined SAR439459 doses and cemiplimab

Geprüfte Regime

  • SAR439459:
    Pharmaceutical form: powder for solution for infusion Route of administration: intravenous infusion
  • Cemiplimab REGN2810:
    Pharmaceutical form: solution for infusion Route of administration: intravenous infusion

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren
Frauenselbsthilfe Krebs unterstützt Menschen mit Krebs auch während der Corona-Krise
Frauenselbsthilfe+Krebs+unterst%C3%BCtzt+Menschen+mit+Krebs+auch+w%C3%A4hrend+der+Corona-Krise
©Photographee.eu - stock.adobe.com

Die Diagnose Krebs ist für die meisten Menschen ein schwerer Schock. In Corona-Zeiten kommt nun auch noch die Angst hinzu, dass die medizinische Versorgung nicht so gut sein könnte, wie sie es in normalen Zeiten in Deutschland ist. Gerade in dieser Situation brauchen die Betroffenen starke Partner an ihrer Seite. Zu diesen zählt Deutschlands größte und älteste Krebs-Selbsthilfe-Organisation, die...

EHA 2021
  • SCD: Häufigere und längere VOC-bedingte Krankenhausaufenthalte nach Vorgeschichte von VOC-Hospitalisierungen – Ergebnisse einer Beobachtungsstudie
  • Real-World-Daten des ERNEST-Registers untermauern Überlebensvorteil unter Ruxolitinib bei primärer und sekundärer Myelofibrose
  • I-WISh-Studie: Ärzte sehen TPO-RAs als beste Option, um anhaltende Remissionen bei ITP-Patienten zu erzielen
  • Phase-III-Studie REACH2 bei steroidrefraktärer akuter GvHD: Hohes Ansprechen auf Ruxolitinib auch nach Crossover
  • SCD: Neues digitales Schmerztagebuch zur tagesaktuellen Erfassung von VOCs wird in Beobachtungsstudie geprüft
  • Französische Real-World-Studie: Eltrombopag meist frühzeitig nach ITP-Diagnose im Rahmen eines Off-label-Use eingesetzt
  • Fortgeschrittene systemische Mastozytose: Französische Real-World-Studie bestätigt klinische Studiendaten zur Wirksamkeit von Midostaurin
  • CML-Management weitgehend leitliniengerecht, aber verbesserungsfähig – Ergebnisse einer Querschnittsbefragung bei britischen Hämatologen
  • Britische Real-World-Studie: Kardiovaskuläres Risikomanagement bei MPN-Patienten in der Primärversorgung nicht optimal
  • Myelofibrose: Früher Einsatz von Ruxolitinib unabhängig vom Ausmaß der Knochenmarkfibrose