Clinical trial NCT04052204: Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors
Official title: A Phase 1b/2 Study to Evaluate Safety and Clinical Activity of Avelumab in Combination With Bempegaldesleukin(NKTR-214) With or Without Talazoparib or Enzalutamide in Participants With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: EMD Serono
name: Nektar Therapeutics
name: Astellas Pharma Inc
First posted: 2019-08-09
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Combination A: Avelumab + Bempegaldesleukin (NKTR-214) for treatment of locally recurrent (not amendable for treatment with curative intent) or metastatic squamous cell carcinoma of the head and neck

Combination B: Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will enroll participants with DDR defect positive mCRPC.

Combination C: Avelumab + Bempegaldesleukin (NKTR-214) + Enzalutamide for Treatment of mCRPC
Primary purpose: TREATMENT

Brief summary: Evaluation of the combination of avelumab + bempegaldesleukin (NKTR-214 ) in locally advanced squamous cell carcinoma of the head and neck ( metastatic SCCHN) and avelumab + bempegaldesleukin (NKTR-214) + talazoparib or enzalutamide in metastatic castration resistant prostate cancer (mCRPC).

Detailed description: Phase 1b/ Phase 2 Design

Phase 1b will be the sequential dose-finding study.

Once the Phase 1b component is completed, Phase 2 will be initiated to further evaluate the safety and anti-tumor activity across combinations of therapy.

Combination A will enroll participants with SCCHN.

Combination B and C will enroll participants with mCRPC

Eligibility criteria: Inclusion Criteria:

* Participants must be ≥ 18 years old.
* Participants with SCCHN or mCRCP.
* Participants must have histological diagnosis of solid tumors and provide tumor tissue.
* Measurable disease by RECIST v1.1 with at least 1 measurable lesion.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
* Adequate bone marrow, renal and liver function
* Highly effective contraceptive use by men with the ability to father a child or women of childbearing potential.
* A WOCBP must have a negative highly sensitive pregnancy test (\[urine or serum\] as required by local regulations) at C1D1.
* Signed and dated informed consent.

Exclusion Criteria:

* Known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monocolonal antibodies.
* Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis.
* Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
* Prior organ transplantation including allogenic stem cell transplantation.
* Vaccination within 4 weeks prior to C1D1 and while on trial is prohibited except for administration of inactivated vaccines.
* Known symptomatic brain lesions requiring steroids.
* Known history of testing positive for human immunodeficiency virus (HIV or known acquired immunodeficiency syndrome (AIDS).
* Positive HBV surface antigen or HCV test indicating acute or chronic infection..
* Active infection requiring systemic therapy
* Clinically significant (i.e., active) cardiovascular disease including the following: documented left ventricular ejection fraction (LVEF) \<50% by ECHO/MUGA; cerebral vascular accident/stroke or transient ischemic attack; myocardial infarction; unstable angina; congestive heart failure or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication.
* Diagnosis of any other malignancy within 2 years prior to C1D1, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix and for Combination A only, low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or castration) or adequately treated prostate cancer.
* Current use of immunosuppressive medication at the time of study enrollment.
* Major surgery within 4 weeks prior to study enrollment.
* Conditions that may impair intake or absorption such as inability to swallow capsules or tablets; known malabsorption syndrome; or baseline diarrhea ≤ Grade 1.
* Participation in other studies involving investigational drug(s) within 2 weeks prior to C1D1.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLT)
timeFrame: Cycle 1 of the treatment period (28 days)
Secondary outcomes:
measure: Duration of Response (DR)
timeFrame: Approximately 8 months (246 days).
measure: Time to Tumor Response (TTR)
timeFrame: Approximately 8 months (246 days).
measure: Progression-Free Survival (PFS)
timeFrame: Approximately 8 months (246 days).
measure: Overall Survival (OS)
timeFrame: Approximately 8 months (246 days).
measure: Pharmacokinetic (PK) Parameters - Cmax and Ctrough for Avelumab and NKTR-214
timeFrame: Blood samples were collected on Day 1 and Day 15 in Cycle 1 and Cycle 2 for avelumab. Blood samples were collected on Day 1, Day 3, Day 4 and Day 8 in Cycle 1, Day1 and Day 8 in Cycle 2 for NKTR-214.
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) Results
timeFrame: Day 1 of Cycle 1, 2 and end of treatment (EOT).
measure: Number of Participants With Positive Neutralizing Antibody (nAb) Results
timeFrame: Day 1 of Cycle 1, 2 and EOT
measure: PD-L1 Expression Level in Baseline and On-treatment Tumor Tissue
timeFrame: On-treatment biopsy is required to be collected on Cycle 1 between Days 9 and 14 for participants in Combination A.
measure: Number of Participants With Treatment-Emergent Adverse Events(TEAEs), Serious TEAEs, TEAEs Leading to Death and Infusion-Related Reactions (IRRs) During On-treatment Period
timeFrame: Approximately 6 months (190 days)
measure: Number of Participants With Laboratory Abnormalities With NCI-CTCAE Grade >= 3 - Safety Analysis Set
timeFrame: Day 1, Day 15 of each treatment cycle
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen campus Sint-Augustinus
state: Antwerpen
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
state: Mazowieckie
city: Barcelona
country: Spain
facility: Hospital Quirón Barceloma
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: