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Solid TumorPhase 1NCT02627274

A Study Evaluating Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281 as a Single Agent (Part A) or in Combination With Trastuzumab or Cetuximab (Part B or C)

A Phase 1 study testing RO6874281, Trastuzumab and Cetuximab in people with Solid Tumor and Breast Cancer, run by Hoffmann-La Roche at 26 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This first-in-human, open-label, multicenter, Phase Ia/Ib, adaptive, multiple ascending-dose study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of RO6874281 as a single agent (Part A) or in combination with trastuzumab or cetuximab (Part B or… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RO6874281, Trastuzumab and Cetuximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
26 sitesin 9 countries
Study dates
7 Dec 2015to 10 Nov 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Radiologically measurable and clinically evaluable disease
  • Absence of rapid disease progression or threat to vital organs or critical anatomical sites requiring urgent alternative medical intervention
  • Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment (special requirements apply for Part C; Participants with only one target lesion and no non-target lesions can enroll after documented agreement with the Medical Monitor).
  • Life expectancy of greater than or equal to (>=12) weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • Participants with unilateral pleural effusion (other than non-small cell lung cancer [NSCLC] indication) should fulfill the following criteria for pulmonary and cardiac functions: Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification 0 - 1 level and New York Heart Association (NYHA) classification class 1 or better
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  • Forced expiratory volume 1 (FEV1) >70% and forced vital capacity (FVC) >70% of predicted value; participants with lung metastases should present with DLCO >60% of predicted value
  • Adequate cardiovascular, hematological, liver and renal function
  • All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to grade less than or equal to (<=) 1, except alopecia (any grade) and Grade 2 peripheral neuropathy
  • Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women less than (<) 12 months after menopause
  • For women who are not postmenopausal and have not undergone surgical sterilization: agreement to remain abstinent or use two adequate non-hormonal methods of contraception, including at least one method with a failure rate of <1 percent (%) per year, during the treatment period and for a period of time after the last dose of study drug(s) as defined in the protocol
  • For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least for at least 2 months after the last dose of study treatment
  • For Part A exclusively (RO6874281 monotherapy), confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of location accessible to biopsy per clinical judgment of the treating physician, and confirmed progression at baseline; for whom no standard therapy that would confer clinical benefit to the participant exists
  • For Part B exclusively (RO6874281 in combination with trastuzumab), participants with metastatic or recurrent or locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer, as defined by the College of American Pathologists HER2 testing guidelines, who have progressed on at least two lines of HER2-directed therapies in the metastatic setting and the last therapy prior to going on study has to contain a HER2-directed antibody; baseline left ventricular ejection fraction (LVEF) of >=50% (measured by echocardiography) predose on Cycle 1 Day 1
  • For Part C exclusively (RO6874281 in combination with cetuximab), participants with recurrent, unresectable or metastatic squamous cell carcinoma of the head and neck. Participants can have had standard or experimental treatment, including but not limited to radiation therapy, chemotherapy, or immunotherapy
  • Participants with Gilbert's syndrome will be eligible for the study

Who cannot join

  • History of, active, or suspicion of autoimmune disease (exceptions apply)
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade 1, except for alopecia, vitiligo, or endocrinopathies managed with replacement therapy
  • Symptomatic or untreated central nervous system (CNS) metastases
  • History of treated asymptomatic CNS metastases with any of the following: Metastases to the brain stem, midbrain, pons, medulla, cerebellum, or within 10 millimeters (mm) of the optic nerves and chiasm; history of intracranial or spinal cord hemorrhage; lacking radiographic demonstration of improvement upon the completion of CNS-directed therapy and evidence of progression between completion of therapy and the baseline radiographic study; ongoing requirement for dexamethasone; stereotactic or whole brain radiation within 28 days before the start of study treatment; last CNS radiographic study less than 4 weeks since completion of radiotherapy and less than 2 weeks since the discontinuation of corticosteroids; CNS metastases treated by resection or brain biopsy performed within 28 days before the start of study treatment
  • Participants with an active second malignancy
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases or other disease with ongoing fibrosis
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  • Participants (all indications) with confirmed bilateral pleural effusion and NSCLC participants with confirmed uni- or bilateral pleural effusion by X-ray are not eligible
  • Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration
  • Active or uncontrolled infections
  • Known human immunodeficiency virus (HIV) or known active hepatitis B virus or hepatitis C virus infection
  • History of chronic liver disease or evidence of hepatic cirrhosis
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Major surgery or significant traumatic injury <28 days prior to the first RO6874281 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Dementia or altered mental status that would prohibit informed consent
  • Pregnant or breastfeeding women
  • Known hypersensitivity to any of the components of RO6874281
  • Concurrent therapy with any other investigational drug
  • Immune-related endocrinopathies
  • Immunomodulating agents <28 days prior to first dose of study drug
  • Treatment with systemic immunosuppressive medications
  • Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy
  • For Part B exclusively, known hypersensitivity to any of the components of trastuzumab
  • For Part C exclusively, known hypersensitivity to any of the components of cetuximab
  • For Parts A, B, and C, eligibility of participants who require blood transfusion before and after the start of the study treatment should be discussed by the Sponsor and investigator
  • For Parts B and C, Participant eligibility for treatment with trastuzumab or cetuximab should be verified against trastuzumab or cetuximab labeling documents.

Trial locations and contacts

26 sites in 9 countries.

26 sites in 9 countries

United States5 sites

  • The Ohio State University

    Columbus, Ohio, 43210

  • Banner MD Anderson Cancer Center

    Greeley, Colorado, 85234

  • UCSD - Moores Cancer Center

    La Jolla, California, 92037

  • Washington University; Division of Oncology

    St Louis, Missouri, 63110

  • University of Arizona Cancer Center

    Tucson, Arizona, 85719

Other trials in United States

France5 sites

  • Institut Bergonie; Oncologie

    Bordeaux, 33076

  • Centre Georges Francois Leclerc

    Dijon, 21000

  • Centre Leon Berard

    Lyon, 69008

  • Institut Claudius Regaud; Departement Oncologie Medicale

    Toulouse, 31059

  • Institut Gustave Roussy; Sitep

    Villejuif, 94805

Other trials in France

Italy5 sites

  • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

    Meldola, Emilia-Romagna, 47014

  • Fondazione IRCCS Istituto Nazionale dei Tumori;S.S. Trattamento MedicoTumori dellaTesta e delCollo

    Milan, Lombardy, 20133

  • Istituto Europeo di Oncologia; Svil. Nuovi Farmaci per Terapie Innovative

    Milan, Lombardy, 20141

  • Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck

    Milan, Lombardy, 20162

  • Ospedale Policlinico S. Matteo; Phase I Clinical Trial Unit and Experimental Therapy

    Pavia, Lombardy, 27100

Other trials in Italy

United Kingdom3 sites

  • Leicester Royal Infirmary

    Leicester, LE1 5WW

  • Guys and St Thomas NHS Foundation Trust, Guys Hospital

    London, SE1 9RT

  • Christie Hospital

    Manchester, M20 3BG

Other trials in United Kingdom

Canada2 sites

  • Juravinski Cancer Clinic; Department of Oncology

    Hamilton, Ontario, L8V 5C2

  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

Netherlands2 sites

  • Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie

    Amsterdam, 1066 CX

  • Erasmus MC

    Rotterdam, 3015 GD

Other trials in Netherlands

Spain2 sites

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • Clinica Universitaria de Navarra

    Pamplona, Navarre, 31008

Other trials in Spain

Belgium1 site

  • UZ Antwerpen

    Edegem, 2650

Other trials in Belgium

Denmark1 site

  • Rigshospitalet; Onkologisk Klinik

    København Ø, 2100

Other trials in Denmark

About this study

Official title: An Open-Label, Multicenter, Dose-Escalation, Phase Ia/Ib Study to Evaluate Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281, an Immunocytokine Consisting of Interleukin 2 Variant (IL-2v) Targeting Fibroblast Activation Protein-α (FAP), as a Single Agent (Part A) or in Combination With Trastuzumab or Cetuximab (Part B or C)

This first-in-human, open-label, multicenter, Phase Ia/Ib, adaptive, multiple ascending-dose study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of RO6874281 as a single agent (Part A) or in combination with trastuzumab or cetuximab (Part B or C).

Being tested
RO6874281, Trastuzumab, Cetuximab
Medical subject headings
Breast Neoplasms, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RO6874281Drug

    Also called simlukafusp alfa

    RO6874281 will be administered as per the schedule specified under arm description.

  • TrastuzumabDrug

    Also called Herceptin

    Trastuzumab will be administered as per the schedule specified under arm description.

  • CetuximabDrug

    Cetuximab will be administered as per the schedule specified under arm description.

Study groups in NCT02627274
Study groupRoleWhat they receive
Part A: RO6874281 MonotherapyExperimentalDose Escalation: RO6874281 will be administered as an intravenous (IV) infusion. The starting dose regimen of RO6874281 as a single agent will be 5 milligrams (mg) once weekly (QW). Different regimens may be explored based on the emerging safety, PK, and PD data of RO6874281 and may be tested in parallel. Participants will be treated with RO6874281 until disease progression, unacceptable toxicities, or withdrawal of consent. Participants may continue treatment with RO6874281 for a maximum of 24 months.
Receives: Drug: RO6874281
Part B: RO6874281 in Combination with TrastuzumabExperimentalDose Escalation: RO6874281 will be administered as an IV infusion. RO6874281 will be administered QW for the first 4 administrations, then Q2W. The standard dose for trastuzumab will be a loading dose of 6 milligrams per kilogram (mg/kg) followed by a maintenance dose of 4 mg/kg from Cycle 2 in a Q2W regimen. Different regimens may be explored based on the emerging safety, PK, and PD data of RO6874281 and may be tested in parallel. Participants will be treated with RO6874281 in combination with trastuzumab until disease progression, unacceptable toxicities, or withdrawal of consent. Participants may continue treatment with RO6874281 in combination with trastuzumab for a maximum of 24 months.
Receives: Drug: RO6874281; Drug: Trastuzumab
Part C: RO6874281 in Combination with CetuximabExperimentalRO6874281 will be administered as an IV infusion. The starting dose regimen of RO6874281 in combination with cetuximab will be 5 mg QW for the first 4 administrations, then Q2W. Cetuximab will be administered Q2W at 500 milligrams per square meter (mg/m^2). Different regimens may be explored based on the emerging safety, PK, and PD data of RO6874281 and may be tested in parallel. Participants will be treated with RO6874281 in combination with cetuximab until disease progression, unacceptable toxicities, or withdrawal of consent. Participants may continue treatment with RO6874281 in combination with cetuximab for a maximum of 24 months. Extension Phase: The MTD for RO6874281 was determined to be 10mg and therefore patients in the extension will be treated with 10mg RO6874281. Cetuximab and R06874281 will be administered weekly during induction phase (cycle 1 and cycle 2). Both IMPs will be administered Q2W starting in cycle 3.
Receives: Drug: RO6874281; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Dose-Limiting Toxicities (DLTs)

    Measured: Day 1 up to Day 21

  2. Maximum Tolerated Dose (MTD) of RO6874281

    Measured: Day 1 up to Day 21

  3. Optimal Biological Dose (OBD) of RO6874281

    Measured: Day 1 up to Day 21

  4. Recommended Dose for Further Development of RO6874281

    Measured: Day 1 up to Day 21

  5. Systemic Clearance (CL) of RO6874281

    Measured: Day 1 up to 24 months

  6. Volume of Distribution at Steady State (Vss) of RO6874281

    Measured: Day 1 up to 24 months

  7. Area Under the Concentration-Time Curve (AUC) of RO6874281

    Measured: Day 1 up to 24 months

  8. Maximum Observed Serum Concentration (Cmax) of RO6874281

    Measured: Day 1 up to 24 months

Secondary outcomes (14)

  1. Number of T Cells in the Peripheral Blood

    Measured: Day 1 up to 24 months

  2. Number of Natural Killer (NK) Cells in the Peripheral Blood

    Measured: Day 1 up to 24 months

  3. Density of Cluster of Differentiation (CD)8+ Cells in Tumor Samples

    Measured: Day 1 up to 24 months

  4. Density of CD3-/Perforin+ Cells in Tumor Samples

    Measured: Day 1 up to 24 months

  5. Density of CD20 Cells in Tumor Samples

    Measured: Day 1 up to 24 months

  6. Percentage of Participants With Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Measured: Day 1 up to 24 months

  7. Percentage of Participants With Disease Control According to RECIST v1.1

    Measured: Day 1 up to 24 months

  8. Progression-Free Survival (PFS) According to RECIST v1.1

    Measured: Day 1 up to 24 months

  9. Percentage of Participants With Overall Response According to Modified RECIST

    Measured: Day 1 up to 24 months

  10. Percentage of Participants With Disease Control According to Modified RECIST

    Measured: Day 1 up to 24 months

  11. PFS According to Modified RECIST

    Measured: Day 1 up to 24 months

  12. Percentage of Participants With Overall Response According to iRECIST

    Measured: Day 1 up to 24 months

  13. Percentage of Participants With Disease Control According to iRECIST

    Measured: Day 1 up to 24 months

  14. PFS According to iRECIST

    Measured: Day 1 up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2015 (estimated)
  2. Study start7 Dec 2015
  3. Primary completion10 Nov 2022
  4. Study completion10 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02627274
Sponsor's protocol ID
BP29842
Other IDs
2015-002251-97, 2015
Status last verified
Nov 2022
First submitted
26 Nov 2015
Last updated
22 Nov 2022
Results posted
No

Publications

  • Hansen AR, Gomez-Roca CA, Robbrecht DGJ, Verlingue L, Italiano A, Bauman JE, Steeghs N, Prenen H, Fayette J, Spicer J, Niu J, Habigt C, Schneider M, Evers S, Sleiman N, Dejardin D, Ardeshir C, Schmid D, Boetsch C, Charo J, Kraxner A, Teichgraber V, Keshelava N, Bonomi MR. Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2024 Dec 16;30(24):5540-5547. doi: 10.1158/1078-0432.CCR-24-1562.

    PubMed 39422604

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO6874281, Trastuzumab and Cetuximab in people with Solid Tumor and Breast Cancer, run by Hoffmann-La Roche at 26 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, France, Italy, United Kingdom, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Day 1 up to Day 21). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02627274, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2022.

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