Mittwoch, 21. April 2021
Navigation öffnen
Anzeige:
Vectibix
JOURNAL ONKOLOGIE – STUDIE

A Study of Autogene Cevumeran (RO7198457) as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors

Rekrutierend

NCT-Nummer:
NCT03289962

Studienbeginn:
Dezember 2017

Letztes Update:
25.03.2021

Wirkstoff:
Atezolizumab, Autogene cevumeran

Indikation (Clinical Trials):
Triple Negative Breast Neoplasms, Kidney Neoplasms, Neoplasm Metastasis

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Genentech, Inc.

Collaborator:
BioNTech SE

Studienleiter

Clinical Trials
Study Director
Hoffmann-La Roche

Kontakt

Reference Study ID Number: GO39733 www.roche.com/about_roche/roche_worldwide.htm
Kontakt:
Phone: 888-662-6728 (U.S. and Canada)
E-Mail: global-roche-genentech-trials@gene.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 38)

Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
45122 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
LungenClinic Großhansdorf GmbH
22927 Großhansdorf
(Schleswig-Holstein)
GermanyAktiv, nicht rekrutierend» Google-Maps
Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Fachklinik für Lungenerkrankungen
34376 Immenhausen
(Hessen)
GermanyRekrutierend» Google-Maps
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
55101 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
HonorHealth Research Institute - Bisgrove
85258 Scottsdale
United StatesRekrutierend» Google-Maps
The Los Angeles Clinic
90025 Los Angeles
United StatesRekrutierend» Google-Maps
UCSF Comprehensive Cancer Ctr
94158 San Francisco
United StatesRekrutierend» Google-Maps
Stanford Cancer Center
94305-5820 Stanford
United StatesRekrutierend» Google-Maps
University of Colorado
80045-2517 Aurora
United StatesRekrutierend» Google-Maps
Yale University Cancer Center, Smilow Cancer Hospital; Medical Oncology
06511 New Haven
United StatesRekrutierend» Google-Maps
Georgetown University
20007 Washington
United StatesRekrutierend» Google-Maps
Massachusetts General Hospital.
02114 Boston
United StatesRekrutierend» Google-Maps
Beth Israel Deaconess Medical Center
02215 Boston
United StatesZurückgezogen» Google-Maps
Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
89169 Las Vegas
United StatesRekrutierend» Google-Maps
Columbia University Medical Center; Clinical Research Management Office
10032 New York
United StatesRekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
University of Oklahoma Health Sciences Center
73104 Oklahoma City
United StatesRekrutierend» Google-Maps
Providence Oncology and Hematology Care Eastside
97213 Portland
United StatesRekrutierend» Google-Maps
University of Pittsburgh Medical Center
15213 Pittsburgh
United StatesAbgeschlossen» Google-Maps
Sarah Cannon Res Inst; TN Onc
37203 Nashville
United StatesRekrutierend» Google-Maps
Seattle Cancer Care Alliance
98109 Seattle
United StatesRekrutierend» Google-Maps
The Ottawa Hospital Cancer Centre; Oncology
K1H 8L6 Ottawa
CanadaRekrutierend» Google-Maps
Princess Margaret Cancer Center
M5G 2M9 Toronto
CanadaRekrutierend» Google-Maps
Antoni van Leeuwenhoek Ziekenhuis
1066 CX Amsterdam
NetherlandsRekrutierend» Google-Maps
Universitair Medisch Centrum Utrecht
3584 CX Utrecht
NetherlandsRekrutierend» Google-Maps
Clinica Universitaria de Navarra; Servicio de oncología
31008 Pamplona
SpainRekrutierend» Google-Maps
Hospital Univ Vall d'Hebron; Servicio de Oncologia
08035 Barcelona
SpainRekrutierend» Google-Maps
Karolinska Hospital; Oncology - Radiumhemmet
171 76 Stockholm
SwedenRekrutierend» Google-Maps
Akademiska sjukhuset, Onkologkliniken
751 85 Uppsala
SwedenRekrutierend» Google-Maps
Barts & London School of Med; Medical Oncology
EC1A 7BE London
United KingdomRekrutierend» Google-Maps
Southampton General Hospital; Medical Oncology
SO16 6YD Southampton
United KingdomRekrutierend» Google-Maps
The Royal Marsden Hospital
SM2 5PT Sutton
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a Phase 1a/1b, open-label, multicenter, global, dose-escalation study designed to

evaluate the safety, tolerability, immune response, and pharmacokinetics of autogene

cevumeran (RO7198457) as a single agent and in combination with atezolizumab (MPDL3280A, an

engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Life expectancy greater than or equal to (>=12 weeks)

- Adequate hematologic and end-organ function

- Measured or calculated creatinine clearance >=50 milliliters per minute (mL/min) on

the basis of the Cockcroft-Gault glomerular filtration rate estimation

Cancer-Specific Inclusion Criteria:

- Participants with histologic documentation of locally advanced, recurrent, or

metastatic incurable malignancy that has progressed after at least one available

standard therapy; or for whom standard therapy has proven to be ineffective or

intolerable, or is considered inappropriate; or for whom a clinical trial of an

investigational agent is a recognized standard of care

- Participants with confirmed availability of representative tumor specimens in

formalin-fixed, paraffin-embedded (FFPE) blocks (preferred), or sectioned tissue

- Participants with measurable disease per RECIST v1.1

Additional Inclusion Criteria for Participants in Each Indication-Specific

Exploration/Expansion Cohort of Phase 1b:

- NSCLC Cohorts (CIT-Naive): Participants with histologically confirmed incurable,

advanced NSCLC not previously treated with anti-PD-L1/PD-1 and/or with anti-CTLA-4

(investigational or approved), for whom a clinical trial of an investigational agent

in combination with an anti-PD-L1/PD-1 antibody is considered an acceptable treatment

option (if CIT [including anti-PD-L1/PD-1 agents] is approved as treatment for NSCLC

by local regulatory authorities).

- NSCLC Cohort (CIT-Treated): Participants with histologically confirmed incurable,

advanced NSCLC previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4

(investigational or approved)

- Triple negative breast cancer (TNBC) Cohort (CIT-Naive): Participants with

histologically confirmed incurable, advanced estrogen receptor (ER)-negative,

progesterone receptor-negative, and human epidermal growth factor receptor 2

(HER2)-negative adenocarcinoma of the breast (triple-negative) not previously treated

with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)

- Colorectal cancer (CRC) Cohort (CIT-Naive): Participants with histologically confirmed

incurable, advanced adenocarcinoma of the colon or rectum not previously treated with

anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)

- Head and neck squamous cell carcinoma (HNSCC) Cohort (CIT-Naive): Participants with

histologically confirmed inoperable, locally advanced or metastatic, recurrent, or

persistent HNSCC (oral cavity, oropharynx, hypopharnyx, or larynx) not amenable to

curative therapy not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4

(investigational or approved)

- Urothelial carcinoma (UC) Cohort (CIT-Naive): Participants with histologically

confirmed incurable, advanced transitional cell carcinoma of the urothelium including

renal pelvis, ureters, urinary bladder, and urethra, not previously treated with

anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved), for whom a

clinical trial of an investigational agent in combination with an anti-PD-L1 antibody

is considered an acceptable treatment option, if CIT (including anti-PD-L1/PD-1

agents) is approved as treatment for UC by local regulatory authorities

- UC Cohort (CIT-Treated): Participants with histologically confirmed incurable advanced

transitional cell carcinoma of the urothelium (including renal pelvis, ureters,

urinary bladder, and urethra) previously treated with anti-PD-L1/PD-1 with or without

anti-CTLA-4 (investigational or approved)

- Renal cell carcinoma (RCC) Cohort (CIT-Naive): Participants with histologically

confirmed incurable, advanced RCC with component of clear cell histology and/or

component of sarcomatoid histology not previously treated with anti-PD-L1/PD-1 and/or

anti-CTLA-4 (investigational or approved)

- Melanoma Cohort (CIT-Naive in metastatic setting): Participants with histologically

confirmed incurable, advanced melanoma not previously treated with anti-PD-L1/PD-1

and/or anti-CTLA-4 (investigational or approved) in the metastatic setting

- Melanoma Cohort (CIT-Treated): Participants with histologically confirmed incurable,

advanced melanoma previously treated with anti-PD-L1/ or PD-1 with or without CTLA-4

(investigational or approved)

Additional Inclusion Criteria for Participants in the Serial-Biopsy Expansion Cohort of

Phase 1b:

- Participants must have one of the locally advanced or metastatic solid tumor types

specified in the protocol.

- Participants must have accessible lesion(s) that permit a total of two to three

biopsies (pretreatment and on-treatment) or one biopsy (on-treatment, if archival

tissue can be submitted in place of a pre-treatment biopsy) without unacceptable risk

of a significant procedural complication. RECIST lesions should not be biopsied.

Exclusion Criteria:

- Known clinically significant liver disease, including active viral, alcoholic, or

other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse

- Major surgical procedure within 28 days prior to Cycle 1, Day 1, or anticipation of

need for a major surgical procedure during the course of the study

- Any other diseases, metabolic dysfunction, physical examination finding, and/or

clinical laboratory finding giving reasonable suspicion of a disease or condition that

contraindicates the use of an investigational drug or that may affect the

interpretation of the results or may render the participant at high risk from

treatment complications

- Previous splenectomy

- Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative

severe combined immunodeficiency [SCID]) or combined T- and B-cell immunodeficiencies

(e.g., T- and B-negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common

variable immunodeficiency)

- Any medical condition or abnormality in clinical laboratory tests that, in the

investigator's judgment, precludes the participant's safe participation in and

completion of the study Cancer-Specific Exclusion Criteria

- Any anti-cancer therapy, whether investigational or approved, including chemotherapy,

hormonal therapy, and/or radiotherapy, within 3 weeks prior to initiation of study

treatment, with the exceptions as mentioned in the protocol

- Eligibility based on prior treatment with CIT depends on the mechanistic class of the

drug and the cohort for which the participant is being considered, as described below.

In addition, all criteria pertaining to adverse events attributed to prior cancer

therapies must be met

All Cohorts (Dose-Escalation in Phase 1a and Dose-Escalation, Backfill, and Expansion in

Phase 1b):

- Prior neoantigen-specific or whole-tumor cancer vaccines are not allowed, with the

exception as specified in protocol

- Prior treatment with cytokines is allowed provided that at least 6 weeks or 5

half-lives of the drug, whichever is shorter, have elapsed between the last dose and

the proposed Cycle 1, Day 1

- Prior treatment with immune checkpoint inhibitors, immunomodulatory monoclonal

antibody (mAbs), and/or mAb-derived therapies is allowed provided that at least 6

weeks (Phase 1a) or 3 weeks (Phase 1b) have elapsed between the last dose and the

proposed Cycle 1, Day 1, with the exceptions as specified in protocol Phase Ib

Dose-Exploration/Expansion Group Only Cohorts

- In the non-melanoma CIT-Naive expansion cohort in Phase Ib, prior treatment with

anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved), is not allowed.

- In the melanoma CIT-naive in metastatic setting expansion cohort in Phase Ib, prior

treatment with anti-PD- L1/PD-1 and/or anti-CTLA-4 (investigational or approved) is

not allowed. Prior anti-PD-L1/PD-1 and/or anti-CTLA-4 therapy in the adjuvant setting

is allowed provided that there is at least a 6-month treatment-free interval between

completion of adjuvant therapy and Cycle 1, Day 1.

- Prior treatment with immunomodulators, including toll-like receptor (TLR) agonists,

inhibitors of indoleamine 2,3-dioxygenase (IDO)/ tryptophan-2,3-dioxygenase (TDO), or

agonists of OX40, is allowed provided that at least 5 half-lives of the drug or a

minimum of 3 weeks have elapsed between the last dose of the prior treatment and the

proposed Cycle 1, Day 1, with the exception as specified in protocol

- Any history of an immune-mediated Grade 4 adverse event attributed to prior CIT (other

than endocrinopathy managed with replacement therapy or asymptomatic elevation of

serum amylase or lipase)

- Any history of an immune-mediated Grade 3 adverse event attributed to prior CIT (other

than hypothyroidism managed with replacement therapy) that resulted in permanent

discontinuation of the prior immunotherapeutic agent and/or occurred less than or

equal to (<=) 6 months prior to Cycle 1 Day 1

- Adverse events from prior anti-cancer therapy that have not resolved to Grade <=1

except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy

- All immune-mediated adverse events related to prior CIT (other than endocrinopathy

managed with replacement therapy or stable vitiligo) must have resolved completely to

baseline

- Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active

CNS metastases (progressing or requiring corticosteroids for symptomatic control)

- Leptomeningeal disease

- Uncontrolled tumor-related pain

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent

drainage procedures

- Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1,

with the exception of those with a negligible risk of metastasis or death

- Uncontrolled hypercalcemia

- Participant has spinal cord compression not definitively treated with surgery and/or

radiation or previously diagnosed and treated spinal cord compression without evidence

that disease has been clinically stable for >=2 weeks prior to screening

Treatment-Specific Exclusion Criteria:

- History of autoimmune disease with caveats as specified in protocol

- Treatment with monoamine oxidase inhibitors (MAOIs) within 3 weeks prior to Cycle 1,

Day 1

- Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1,

Day 1

- History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or

evidence of active pneumonitis on screening chest computed tomography (CT) scan

- Positive test for human immunodeficiency virus (HIV) infection

- Active hepatitis B, hepatitis C

- Known active or latent tuberculosis infection

- Severe infections within 4 weeks prior to Cycle 1, Day 1

- Recent infections not meeting the criteria for severe infections within 2 weeks prior

to Cycle 1, Day 1

- Prior allogeneic bone marrow transplantation or prior solid organ transplantation

- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or

anticipation that such a live attenuated vaccine will be required during the study

- Known hypersensitivity to the active substance or to any of the excipients in the

vaccine

- Phase 1b and crossover only: History of severe allergic, anaphylactic, or other

hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;

Known hypersensitivity to Chinese Hamster Ovary (CHO)-cell products; Allergy or

hypersensitivity to components of the atezolizumab formulation

Studien-Rationale

Primary outcome:

1. Percentage of Participants with Dose-Limiting Toxicities (DLTs) (Time Frame - Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21)

2. MTD/Recommended Phase 2 Dose (RP2D) of Autogene Cevumeran (Time Frame - Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21)

3. Percentage of Participants with Adverse Events (AEs) (Time Frame - Baseline up to end of the study (up to approximately 3 years))

4. Percentage of Participants with Immune-Mediated Adverse Events (imAEs) (Time Frame - Baseline up to end of the study (up to approximately 3 years))

5. Percentage of Participants by Number of Treatment Cycles Received (Time Frame - Baseline up to end of the study (up to approximately 3 years))

6. Dose Intensity of Autogene Cevumeran (Time Frame - Baseline up to end of the study (up to approximately 3 years))

7. Change from Baseline in Targeted Vital Signs (Time Frame - Baseline up to end of study (up to approximately 3 years))

8. Change from Baseline in Targeted Clinical Laboratory Test Results (Time Frame - Baseline up to end of study (up to approximately 3 years))

9. Change from Baseline in ECGs (Time Frame - Baseline up to end of study (up to approximately 3 years))

Secondary outcome:

1. Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST v1.1) (Time Frame - Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years))

2. Duration of Response (DoR) According to RECIST v1.1 (Time Frame - From first occurrence of a documented objective response (CR or PR) until disease progression or death due to any cause, whichever occurs first (up to approximately 3 years))

3. Percentage of Participants with Objective Response of CR or PR According to Immune-Modified RECIST (Time Frame - Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years))

4. DoR According to Immune-Modified RECIST (Time Frame - From first occurrence of a documented objective response (CR or PR) until disease progression or death due to any cause, whichever occurs first (up to approximately 3 years))

5. Progression-Free Survival (PFS) According to RECIST v1.1 (Time Frame - Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years))

6. Overall Survival (OS) (Time Frame - Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years))

7. Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab (Time Frame - Pre-infusion (0 hr) until 2 months post treatment discontinuation (up to approximately 3 years))

Studien-Arme

  • Experimental: Phase 1a Flat Dose Escalation: Autogene Cevumeran
    Participants will receive autogene cevumeran at escalated dosages.
  • Experimental: Phase 1b Flat Dose Escalation: Autogene Cevumeran + Atezolizumab
    Participants will receive autogene cevumeran at escalated dosages along with atezolizumab at a fixed dose of 1200 milligrams (mg)
  • Experimental: Phase Ib: Dose Exploration: Autogene Cevumeran + Atezolizumab
    Non-small cell lung cancer (NSCLC) or melanoma cancer immunotherapy (CIT)-treated participants will receive autogene cevumeran (at dosage lower than maximum tolerated dose [MTD] based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.
  • Experimental: Phase 1b Expansion: Autogene Cevumeran + Atezolizumab
    Participants with different indications as per inclusion criteria will receive autogene cevumeran (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.
  • Experimental: Phase 1b Expansion: Autogene Cevumeran + Atezolizumab (Serial Biopsy)
    CIT-naive patients with selected tumor types who consent to optional serial biopsies will receive autogene cevumeran (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a dixed dose of 1200 mg.

Geprüfte Regime

  • Autogene cevumeran (RO7198457):
    Autogene cevumeran will be administered by intravenous (IV) infusion, in 21-day cycles.
  • Atezolizumab (Tecentriq / RO5541267 / MPDL3280A / An engineered anti-PDL1 antibody / ):
    Atezolizumab will be administered by IV infusion on Day 1 of every 21-day cycle.

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren
Schmerzmittel Methadon ist kein Krebsheilmittel - keine falschen Hoffnungen wecken
Schmerzmittel+Methadon+ist+kein+Krebsheilmittel+-+keine+falschen+Hoffnungen+wecken
@ efmukel / Fotolia.com

Das Opioid Methadon sollte nicht zur Tumortherapie eingesetzt werden. Die derzeit vorliegenden Daten aus Labor- und Tierversuchen sowie einer Studie mit 27 Krebspatienten reichen nicht aus, um eine Behandlung zu rechtfertigen. Einige Medienberichte wecken dennoch bei an Leukämie oder Hirntumor erkrankten Patienten die falsche Hoffnung auf Heilung. Methadon ist zur Behandlung starker Schmerzen zugelassen und ein etabliertes Medikament in...

Vor der Darmspiegelung ist „Abführen an zwei Tagen“ am effektivsten
Vor+der+Darmspiegelung+ist+%E2%80%9EAbf%C3%BChren+an+zwei+Tagen%E2%80%9C+am+effektivsten
© Sebastian Kaulitzki / Fotolia.com

Je sauberer der Darm, umso aussagekräftiger ist das Ergebnis einer Darmspiegelung zur Krebsvorsorge. Darauf weisen Experten im Vorfeld des Kongresses Viszeralmedizin 2016 in Hamburg hin. Um den Darm optimal für die „Koloskopie“ vorzubereiten, sollten Patienten auf zwei Tage verteilt eine Poly-Ethylen-Glykol-Lösung (kurz: PEG) als Abführmittel zu sich nehmen, so die Mediziner. Die Darmspiegelung gilt als eines...

Biopharmazeutika sind den meisten Deutschen unbekannt
Biopharmazeutika+sind+den+meisten+Deutschen+unbekannt
© Darren Baker / Fotolia.com

Naturheilmittel oder neuer Trend der Bio-Welle? 94 Prozent der Deutschen können mit dem Begriff Biopharmazeutika nichts anfangen (1). Oftmals werden hinter dem Begriff Naturheilmittel vermutet. Dabei handelt es sich um Arzneimittel, die biotechnisch hergestellt oder aus gentechnisch veränderten Organismen gewonnen werden und mit dem Ziel der Bekämpfung einer Krankheit in die Vorgänge des Körpers eingreifen. Insulin...