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A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors

Last updated on October 17, 2019

FOR MORE INFORMATION
Study Location
Institut Jules Bordet
Brussels, , 1000 Belgium
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Pancreatic Cancer, Non-Small Cell Lung Cancer, Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
tumors that are not amenable for treatment with curative intent as follows:

1. Stage IIIb/IV NSCLC with documented positive KRAS or NRAS mutation status as
determined using a validated test performed in a College of American Pathologists
(CAP)/Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (or
other comparable local or regional certification); or

2. Metastatic pancreatic ductal adenocarcinoma; or

3. Phase 2 only: other advanced solid tumors with documented positive KRAS or NRAS
mutation as determined using a validated test performed in a CAP/CLIA-certified
laboratory (or other comparable local or regional certification).

- Have had disease progression during or following at least 1 and not more than 2 prior
lines of treatment for advanced or metastatic disease.

- Patients with NSCLC must have previously received treatment with an anti-PD-1 or
anti-PD-L1 agent for advanced disease.

- Measurable disease as per RECIST v1.1 criteria.

- Provision of a baseline tumor sample.

- Age ≥18 years (Japanese patients must be ≥20 years old)

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

- Adequate bone marrow, renal and liver functions.

- Adequate cardiac function.

- Informed consent provided.

Exclusion criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

- Prior treatment with avelumab, a PARP inhibitor or MEK inhibitor.

- Prior systemic anti-cancer therapy within 2 weeks prior to study enrollment.

- Persisting toxicity related to prior therapy.

- Current use of immunosuppressive medication.

- Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis,
pulmonary fibrosis, uveitis or iritis.

- Active or prior autoimmune disease that might deteriorate when receiving an
immunostimulatory agent.

- Diagnosis of myelodysplastic syndrome (MDS).

- Known symptomatic brain metastases requiring steroids.

- Known history of testing positive for HIV or hepatitis.

- Clinically significant (ie, active) cardiovascular disease.

- History of thromboembolic or cerebrovascular events.

- Current or anticipated use of a P-gp inhibitor, inducer, or inhibitor of breast cancer
resistance protein (BCRP)

- Uncontrolled hypertension.

- Concurrent neuromuscular disorder that is associated with the potential of elevated
creatinine kinase.

- Known history of Gilbert's syndrome.

- History or current evidence of retinal degenerative disease, retinal vein occlusion
(RVO) or current risk factors for RVO.

- Other acute or chronic medical or psychiatric condition.

NCT03637491
Pfizer
Not yet recruiting
A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors

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Pfizer Clinical Trials Contact Center

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[email protected]

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Descriptive Information
Brief Title  ICMJE A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors
Official Title  ICMJE A PHASE 1B/2 STUDY TO EVALUATE SAFETY AND CLINICAL ACTIVITY OF AVELUMAB IN COMBINATION WITH BINIMETINIB WITH OR WITHOUT TALAZOPARIB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC RAS-MUTANT SOLID TUMORS
Brief SummaryThis Phase 1b/2 study will examine the effects of the study drugs, avelumab and binimetinib given together (doublet) and in combination with talazoparib (triplet), in patients with locally advanced or metastatic RAS-mutant solid tumors. The Phase 1b part of the study will assess if the different study drugs can be given together safely and which doses to use for further research. Phase 2 will test if the study treatments have an effect on tumor size and growth, and gather more information about potential side effects.
Detailed Description

This is a Phase 1b/2, open label, multi-center, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of avelumab in combination with binimetinib with or without talazoparib in adult patients with locally advanced or metastatic KRAS- or NRAS-mutant non-small cell lung cancer, pancreatic ductal adenocarcinoma, or other KRAS- or NRAS-mutant solid tumors.

The Phase 1b part of this study will initially assess the combination of avelumab and binimetinib (doublet) to determine a recommended dose for further investigation. Following this, the recommended dose for the combination of avelumab, binimetinib and talazoparib (triplet) will be determined. The recommended doses for the doublet and triplet combinations will be used in the Phase 2 part of the study, which will assess the safety and preliminary anti-tumor activity of the study treatments.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Cancer
  • Non-Small Cell Lung Cancer
  • Cancer
Intervention  ICMJE
  • Drug: Avelumab
    IV treatment
    Other Name: MSB0010718C
  • Drug: Binimetinib
    Oral treatment
    Other Names:
    • MEK162
    • ARRY-438162
  • Drug: Talazoparib
    Oral treatment
    Other Name: MDV3800, BMN 673
Study Arms  ICMJE
  • Experimental: Avelumab and binimetinib
    Open label
    Interventions:
    • Drug: Avelumab
    • Drug: Binimetinib
  • Experimental: Avelumab, binimetinib and talazoparib
    Open label
    Interventions:
    • Drug: Avelumab
    • Drug: Binimetinib
    • Drug: Talazoparib
Publications *Not Provided


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 16, 2018)
127
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 4, 2023
Estimated Primary Completion DateMarch 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent as follows:

    1. Stage IIIb/IV NSCLC with documented positive KRAS or NRAS mutation status as determined using a validated test performed in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (or other comparable local or regional certification); or
    2. Metastatic pancreatic ductal adenocarcinoma; or
    3. Phase 2 only: other advanced solid tumors with documented positive KRAS or NRAS mutation as determined using a validated test performed in a CAP/CLIA-certified laboratory (or other comparable local or regional certification).
  • Have had disease progression during or following at least 1 and not more than 2 prior lines of treatment for advanced or metastatic disease.
  • Patients with NSCLC must have previously received treatment with an anti-PD-1 or anti-PD-L1 agent for advanced disease.
  • Measurable disease as per RECIST v1.1 criteria.
  • Provision of a baseline tumor sample.
  • Age ?18 years (Japanese patients must be ?20 years old)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  • Adequate bone marrow, renal and liver functions.
  • Adequate cardiac function.
  • Informed consent provided.

Exclusion Criteria:

  • Prior treatment with avelumab, a PARP inhibitor or MEK inhibitor.
  • Prior systemic anti-cancer therapy within 2 weeks prior to study enrollment.
  • Persisting toxicity related to prior therapy.
  • Current use of immunosuppressive medication.
  • Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, uveitis or iritis.
  • Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
  • Diagnosis of myelodysplastic syndrome (MDS).
  • Known symptomatic brain metastases requiring steroids.
  • Known history of testing positive for HIV or hepatitis.
  • Clinically significant (ie, active) cardiovascular disease.
  • History of thromboembolic or cerebrovascular events.
  • Current or anticipated use of a P-gp inhibitor, inducer, or inhibitor of breast cancer resistance protein (BCRP)
  • Uncontrolled hypertension.
  • Concurrent neuromuscular disorder that is associated with the potential of elevated creatinine kinase.
  • Known history of Gilbert's syndrome.
  • History or current evidence of retinal degenerative disease, retinal vein occlusion (RVO) or current risk factors for RVO.
  • Other acute or chronic medical or psychiatric condition.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Belgium,   Singapore,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03637491
Other Study ID Numbers  ICMJE B9991033
2018-000124-34 ( EudraCT Number )
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product:Yes
Studies a U.S. FDA-regulated Device Product:No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/da....
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/da...
Responsible PartyPfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Array BioPharma
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS AccountPfizer
Verification DateAugust 2019

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

BY PHONE

Pfizer Clinical Trials Contact Center

1-800-718-1021

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Contact

[email protected]

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