Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Avelumab

Axitinib

Immunoglobulins

Endothelial Growth Factors

Mitogens

Palbociclib

Immunoglobulins, Intravenous

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

For the Phase 1:

Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle).

For the Phase 2:

Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.

A human antibody of the immunoglobulin gamma-1 isotype that specifically targets and blocks the Programmed Death ligand (PD-L1) for PD-1.

A selective oral (tablet) inhibitor of tyrosine kinases Vascular Endothelial Growth Factor (VEGF) receptors 1, 2, and 3. These receptors are implicated in pathologic angiogenesis, tumor growth and cancer progression.

A selective, reversible oral (capsule) inhibitor of cyclin-dependent kinases (CDK) 4 and 6. The inhibition of CDK 4/6 blocks DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase.

RAZELLE KURZROCK, MD

Patients with advanced/metastatic non-small cell lung cancer (NSCLC) with no documented targetable alterations (Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic Lymphoma Kinase (ALK) translocation, ROS1 mutation if available or MET exon 14 skipping mutation if available) will receive a tri-therapy associating avelumab, axitinib and palbociclib.

During the Phase 1 (approximately 30 patients), the tri-therapy will be tested at different doses following a specific dose-escalation scheme (3 + 3 model) in order to establish the safety and identify the Maximum Tolerated Dose (MTD) and recommended dose for the Phase 2 (RP2D). The phase 2 will confirm the safety and will assess the clinical utility of the tri-therapy approach in the treatment of advanced/metastatic NSCLC (100 patients). The study will also explore the clinical utility of the Simplified Interventional Mapping System (SIMS), a new tool/algorithm enabling matching of NSCLC patients with combination therapy. For this purpose tumor/metastasis and matched normal tissue biopsies will be requested in order to obtain sequencing and expression profiles.

Survival Prolongation by Rationale Innovative Genomics

A Proof of Concept Study to Explore Safety and Efficacy of Tri-therapy Approach in Advanced/Metastatic NSCLC and Retrospectively Assess the Ability of Integrated Genomics and Transcriptomics to Match Patients to the Combination

The occurrence of adverse events and serious adverse events reported from the signing of an informed consent through 90 days after the last administration of the treatment will be summarized for all subjects who received at least one dose of the study treatment (safety population) and will be evaluated based on NCI CTCAE v4.03: June 14, 2010.

Response rate is defined as the proportion of participants with reduction in tumor burden of a predefined amount based on RECIST 1.1 evaluation

Duration of Response (DR) is defined for patients with confirmed objective response (Complete Response \[CR\] or Partial Response \[PR\]) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

Progression Free Survival (PFS) is defined as the time from the first dose of study treatment to the date of disease progression by RECIST 1.1 or death due to any cause, whichever occurs first.

OS is defined as the time from the first dose of study treatment to the date of death due to any cause.

The proportion of participants whose SIMS analysis matches the treatment combination, will be correlated retrospectively to clinical outcome.

The occurrence of treatment-related and or biopsy-related serious adverse events as assessed by NCI CTCAE v4.03 will be summarized for all study subjects.

Genomic (DNA) and transcriptomic (RNA) aberrations (mutations, translocations, rearrangements and changes in expression level) identified in the study population (Non-Small Cell Lung) will be described.

ARC Foundation for Cancer Research

Pfizer

Worldwide Innovative Network Association

AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Causal relationship between study treatment and AEs was determined by the investigators and the clinical monitoring committee, and events were considered drug-related if classified by the investigator as at least possibly related to study treatment.

Non-small cell lung cancer (NSCLC) patients treated with avelumab (10 mg/kg IV every two weeks -1/+3 days, on day 1 and day 15 of a 28 day cycle), axitinib (3 mg taken orally twice a day, every day of a 28 day cycle) and palbociclib (75 mg taken orally, daily on days 8-28 of a 28 day cycle).

Dose Level 1

Non-small cell lung cancer (NSCLC) patients treated with avelumab (10 mg/kg IV every two weeks -1/+3 days, on day 1 and day 15 of a 28 day cycle), axitinib (5 mg taken orally twice a day, every day of a 28 day cycle) and palbociclib (75 mg taken orally, daily on days 8-28 of a 28 day cycle).

Dose Level 2

Non-small cell lung cancer (NSCLC) patients treated with avelumab (10 mg/kg IV every two weeks -1/+3 days, on day 1 and day 15 of a 28 day cycle), axitinib (5 mg taken orally twice a day, every day of a 28 day cycle) and palbociclib (100 mg taken orally, daily on days 8-28 of a 28 day cycle).

Dose Level 3

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Caucasian

Mexican

Black

Asian

Race/Ethnicity, Customized

United States

Luxembourg

Israel

Spain

Region of Enrollment

The trial was early terminated after the end of its Phase 1 due to lack of funding. As a result it was not possible to analyse the objectives of the study.

Fanny Wunder, Project Manager

100 treated patients in the Phase 2 including patients enrolled in the Phase 1 at the recommended Phase 2 dose. The planned population for analysis of response (evaluable patients) was those that received at least one cycle of treatment.

Planned Population for Analysis

This outcome could not be measured because the data were not collected. Indeed, the trial was early terminated after the end of the phase 1. The phase 2 was not started, no data can be reported.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Survival Prolongation by Rationale Innovative Genomics	NCT03386929	Non-small Cell ... Non-small Cell ...	Avelumab Axitinib Palbociclib	18 Years -	Worldwide Innovative Network Association
Survival Prolongation by Rationale Innovative Genomics	NCT03386929	Non-small Cell ... Non-small Cell ...	Avelumab Axitinib Palbociclib	18 Years -	Worldwide Innovative Network Association
Survival Prolongation by Rationale Innovative Genomics	NCT03386929	Non-small Cell ... Non-small Cell ...	Avelumab Axitinib Palbociclib	18 Years -	Worldwide Innovative Network Association

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