Trial record 1 of 1 for:
03637491
A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors
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| ClinicalTrials.gov Identifier: NCT03637491 |
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Recruitment Status :
Recruiting
First Posted : August 20, 2018
Last Update Posted : December 11, 2019
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
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Brief Summary:
This Phase 1b/2 study will examine the effects of the study drugs, avelumab, binimetinib and talazoparib when given in a 2 (doublet) or 3 (triplet) drug combination, 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pancreatic Cancer | Drug: Avelumab Drug: Binimetinib Drug: Talazoparib | Phase 2 |
This is a Phase 1b/2, open label, multi-center, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of combinations of avelumab, binimetinib and talazoparib in adult patients with metastatic pancreatic ductal adenocarcinoma and other locally advanced or metastatic KRAS- or NRAS-mutant solid tumors.
The Phase 1b part of this study will initially assess doublet drug combinations 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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 122 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A PHASE 1B/2 STUDY TO EVALUATE SAFETY AND CLINICAL ACTIVITY OF COMBINATIONS OF AVELUMAB, BINIMETINIB AND TALAZOPARIB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC RAS-MUTANT SOLID TUMORS |
| Actual Study Start Date : | August 15, 2018 |
| Estimated Primary Completion Date : | April 19, 2023 |
| Estimated Study Completion Date : | October 16, 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Avelumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Avelumab and binimetinib
Open label
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Drug: Avelumab
IV treatment
Other Name: MSB0010718C Drug: Binimetinib Oral treatment
Other Names:
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Experimental: Avelumab, binimetinib and talazoparib
Open label
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Drug: Avelumab
IV treatment
Other Name: MSB0010718C Drug: Binimetinib Oral treatment
Other Names:
Drug: Talazoparib Oral treatment
Other Name: MDV3800, BMN 673 |
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Experimental: Binimetinib and talazoparib.
Open label.
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Drug: Binimetinib
Oral treatment
Other Names:
Drug: Talazoparib Oral treatment
Other Name: MDV3800, BMN 673 |
Primary Outcome Measures :
- Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 (days 1-28 of study treatment) ]Phase 1: DLT during the primary DLT evaluation period (Cycle 1)
- Confirmed Objective Response (OR) [ Time Frame: From start date (date of randomization for randomized cohorts and first dose of study treatment for non-randomized cohorts) until the date of first documentation of progressive disease or death due to any cause assessed up to approximately 24 months. ]Phase 2: Confirmed OR, defined as a complete response (CR) or partial response (PR) per RECIST v1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met.
Secondary Outcome Measures :
- Concentration of avelumab in blood [ Time Frame: Day 1, Day 8 and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12. ]Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
- Concentration of avelumab in blood [ Time Frame: Day 1, Day 8 and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12. ]Pharmacokinetic parameters: post dose concentrations (Cmax)
- Avelumab ADA levels [ Time Frame: Day 1, Day 8 and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12. ]Immunogenicity assessment of avelumab
- Neutralizing antibodies (nAb) against avelumab. [ Time Frame: Day 1, Day 8 and Day 15 of Cycle 1 (each cycle is 28 days); Day 1 and Day 15 of Cycle 2; and Day 1 of Cycles 3, 5, 9 and 12. ]Immunogenicity assessment of avelumab
- Concentration of binimetinib in plasma [ Time Frame: Pre-dose on Day 1, Day 8 and Day 15 of Cycle 1 (each cycle is 28 days). Day 1 of Cycle 2 and 3 ]Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
- Concentration of binimetinib in plasma [ Time Frame: Day 1, Day 8 and Day 15 of Cycle 1 (each cycle is 28 days). Day 1 of Cycle 2 and Cycle 3. ]Pharmacokinetic parameters: post dose concentrations (Cmax).
- Concentration of talazoparib in plasma [ Time Frame: Pre-dose on Day 1, 8 and Day 15 of Cycle 1 (each cycle is 28 days), and on Day 1 of Cycle 2 and 3 ]Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
- Biomarker Tumor Mutational Burden [ Time Frame: Baseline ]Tumor mutational burden in baseline tumor tissue
- Biomarker PD-L1 [ Time Frame: Baseline ]PD-L1 expression level in baseline tumor tissue.
- Biomarker DNA Damage Repair [ Time Frame: Baseline ]DDR gene alterations in baseline tumor tissue.
- Objective Response [ Time Frame: From the start of treatment until disease progression/recurrence up to approximately 24 months. ]Phase 1b: Confirmed OR based on Investigator assessment per RECIST v1.1.
- Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 24 months ]TTR is defined, for patients with an OR, as the time from the 'start date' to the first documentation of objective response (CR or PR) which is subsequently confirmed
- Duration of Response (DR) [ Time Frame: Baseline up to approximately 24 months ]DR is defined, for patients with OR, as the time from the first documentation of objective response (CR or PR) to the date of first documentation of PD or death due to any cause
- Overall Survival (OS) [ Time Frame: Baseline up to approximately 24 months ]OS is defined as the time from time from the 'start date' to the date of death due to any cause. Patients without an event (death) will be censored at the date of last contact
- Progression Free Survival [ Time Frame: Baseline up to approximately 24 months ]PFS is defined as the time from 'start date' to the date of PD by RECIST v1.1 or death due to any cause, whichever occurs first
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent as follows:
- Metastatic pancreatic ductal adenocarcinoma; or
- Phase 2 only: Stage IIIb/IV NSCLC or 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03637491
Contacts
| Contact: Pfizer CT.gov Call Center | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Locations
Show 19 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT03637491 |
| Other Study ID Numbers: |
B9991033 2018-000124-34 ( EudraCT Number ) |
| First Posted: | August 20, 2018 Key Record Dates |
| Last Update Posted: | December 11, 2019 |
| Last Verified: | December 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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/data_requests. |
| URL: | https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Pfizer:
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KRAS NRAS PDAC Pancreatic Cancer |
Additional relevant MeSH terms:
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Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases |
Talazoparib Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |