Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Squamous Cell

Prostatic Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Antibodies

Antibodies, Monoclonal

Androgens

Avelumab

Immunoglobulins

Adenosine

Talazoparib

Androgen Receptor Antagonists

Antineoplastic Agents, Immunological

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

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

Avelumab + Bempegaldesleukin (NKTR-214) + Talazoparib for treatment of metastatic castration-resistant prostate cancer (mCRPC). Phase 2 will focus on enrolling participants with DDR defect positive mCRPC.

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

Investigational fully human anti-PD-L1 monoclonal antibody

avelumab

Investigational CD122-biased cytokine agonist

Bempegaldesleukin

poly (adenosine diphosphate \[ADP\] ribose) polymerase (PARP) inhibitor

talazoparib

enzalutamide

Pfizer CT.gov Call Center

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).

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

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

Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors

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

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.

DLTs were graded according to NCI- CTCAE version 4.03 and coded using the latest version of Medical Dictionary for Regulatory Activities (MedDRA) preferred term (PT) as event category and MedDRA primary system organ class (SOC) body term as Body System category.

DR was defined, for participants with a confirmed Objective Response (OR), as the time from the first documentation of OR to the date of first documentation of progressive disease (PD) or death due to any cause. The documentation of PD was defined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. If a subject had not had an event (PD or death), DR was censored at the date of last adequate tumor assessment.

As there were no objective responses in the study, no participant met the definition of analysis population.

TTR was defined, for participants with objective response, as the time from the date of first dose of study treatment to the first documentation of objective response (Complete Response or Partial Response) which was subsequently confirmed.

As there were no objective responses in the study, no participant met the definition of analysis population.

Progression-Free Survival (PFS) was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurred first. PFS data were censored on the date of the last adequate tumor assessment for participants who did not have an event (PD or death), for participants who started new anti-cancer therapy prior to an event, or for participants with an event after two or more missing tumor assessments. Participants who did not have an adequate baseline tumor assessment or who did not have any adequate post-baseline tumor assessments were censored on the date of first dose of study treatment unless death occurred on or before the time of the second planned tumor assessment, in which case the death was considered an event. PFS time was summarized using the Kaplan-Meier method.

Overall survival (OS) was defined as the time from the date of first dose of study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact.

OS time was summarized using the Kaplan-Meier method.

Cmax was defined as the maximum observed plasma concentration at the end of infusion. Ctrough was defined as the predose concentration at the end of dosing interval.

ADA against avelumab and NKTR-214 in serum samples was determined and reported separately for ADA never-positive, ADA ever-positive participants, baseline ADA positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, persistent ADA response. For all participants, blood for ADA samples was drawn from the contralateral arm of the avelumab and NKTR-214 infusion.

nAb in serum samples was determined and reported separately for nAb never-positive, nAb ever-positive, baseline nAb positive, treatment-induced nAb, transient nAb response, persistent nAb response.

PD-L1 expression level in baseline tumor tissue, and in on-treatment tumor tissue was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and/or inflammatory cells in regions of interest. PD-L1 expression level in baseline tumor tissue and in on-treatment tumor tissue were under pathological analyses, assisted by image analysis. Participants were classified as positive or negative according to scoring algorithms and cut-offs established from internal or external sources.

Adverse events (AEs) were any untoward medical occurrences in a participant or clinical study participants, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent adverse events (TEAEs) were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment). A Serious Adverse Event (SAE) was defined as any untoward medical occurrence that, at any dose: a. Results in death, b. Was life-threatening, c. Required inpatient hospitalization or prolongation of existing hospitalization, d. Resulted in persistent disability/incapacity, e. Was a congenital anomaly/birth defect. Causality to study treatment was determined by the investigator.

Liver Function Tests of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) were used to assess possible drug induced liver toxicity. The number of participants with at least one of the following laboratory results were summarized below: 1. (ALT ≥3 × ULN or AST ≥3 × ULN) post-baseline. 2. TBILI ≥2 × ULN post-baseline. 3. (ALP ≤2 × ULN or missing) post-baseline.

EMD Serono

Nektar Therapeutics

Astellas Pharma Inc

Pfizer

NKTR-214 was administered prior to avelumab. NKTR-214 0.006 mg/kg was administered intravenously (IV) over 30 minutes every 2 weeks (Q2W). Avelumab 800 mg as a 1-hour IV infusion was administered after the NKTR-214 Q2W, at the investigational site on an outpatient basis on Day 1 and Day 15 of each 28-day cycle. Within the 2-day window, avelumab and NKTR-214 were administered on the same day. Dose reduction of NKTR-214 to 0.003 mg/kg Q2W was triggered if higher than expected toxicity is observed at the higher dose (risk of excessive toxicity ≥ 0.25).

Avelumab + Bempegaldesleukin (NKTR-214) (Combination A)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Phase 1b part of Combination A was conducted but not completed as company terminated this study on 21 May 2021. Termination was not due to a regulatory request or new emerging safety signals. Test for Combination B, Combination C and Phase 2 expansion for Combination A planned in the protocol were not conducted.

Pfizer ClinicalTrials.gov Call Center

The DLT-evaluable analysis set included all enrolled participants in Phase 1b who receive at least one dose of the combination treatment and either experience DLT during the first cycle (28 days) of treatment, or complete the DLT observation period for the first cycle of treatment without a DLT.

Number of Participants With Dose Limiting Toxicities (DLT)

All participants treated in combination A who achieved an OR.

Duration of Response (DR)

Time to Tumor Response (TTR)

All participants treated in Combination A.

Progression-Free Survival (PFS)

Overall Survival (OS)

The PK parameter analysis set was a subset of the safety analysis set and included participants who had at least one of the PK parameters of interest for avelumab, NKTR-214, IL-2, talazoparib, enzalutamide, or N-desmethyl-enzalutamide.

Pharmacokinetic (PK) Parameters - Cmax and Ctrough for Avelumab and NKTR-214

The immunogenicity analysis set was a subset of the safety analysis set and included participants who had at least one ADA/nAb sample collected for avelumab, NKTR-214, or IL-2.

Number of Participants With Positive Anti-Drug Antibody (ADA) Results

Number of Participants With Positive Neutralizing Antibody (nAb) Results

The biomarker analysis set for biomarkers that were only measured at screening was a subset of the safety analysis set and included participants who had at least one baseline biomarker assessment.

PD-L1 Expression Level in Baseline and On-treatment Tumor Tissue

Participants with all-causality TEAEs

Participants with grade ≥ 3 all-causality TEAEs

Participants with treatment-related TEAEs

Participants with grade ≥ 3 treatment-related TEAEs

Participants with serious all-causality TEAEs

Participants with serious treatment-related TEAEs

Participants with all-causality TEAEs leading to death

Participants with treatment-related TEAEs leading to death

Participants with IRRs

The safety analysis set included all participants who received at least one dose of study drug.

Number of Participants With Treatment-Emergent Adverse Events(TEAEs), Serious TEAEs, TEAEs Leading to Death and Infusion-Related Reactions (IRRs) During On-treatment Period

Number of Participants With Laboratory Abnormalities With NCI-CTCAE Grade >= 3 - Safety Analysis Set

The dose level for avelumab was fixed at 800 mg Q2W. The starting dose level for NKTR-214 and talazoparib was determined at the completion of the dose finding for Combination A based on available clinical data. The lowest allowed dose for NKTR-214 was 0.003 mg/kg and the lowest allowed dose for talazoparib was 0.5 mg once daily, in which case participants with moderate renal impairment cannot be enrolled. NKTR-214 was administered prior to avelumab. Talazoparib was taken at the clinic after all procedures/assessments completed, before or after the NKTR-214 and avelumab infusions.

Arm was not tested as company terminated this study on 21 May 2021.

Avelumab + NKTR-214+ Talazoparib (Combination B)

The dose level for avelumab was fixed at 800 mg Q2W. The starting dose level for NKTR-214 and enzalutamide was determined at the completion of the dose finding for Combination A based on available clinical data. The approved label dose for enzalutamide was 160 mg once daily (QD) unless unexpected safety issues requiring it lowering according to the Bayesian Logistic Regression Model (BLRM) recommendation. NKTR-214 was administered prior to avelumab. The daily dose of enzalutamide was taken at the clinic after all procedures/assessments completed, and before or after the avelumab and NKTR-214 infusions.

Arm was not tested as company terminated this study on 21 May 2021.

Spots Global Cancer Trial Database for Avelumab With Bempegaldesleukin With or Without Talazoparib or Enzalutamide in Advanced or Metastatic Solid Tumors

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