Survival Prolongation by Rationale Innovative Genomics

NCT03386929 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: WIN0012017-001455-32
• Study Type: interventional
• Target: 15
• Locations: 4 countries
• Sites: 5

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer Metastatic; Non-small Cell Lung Cancer Stage IIIB

Keywords

NSCLC; tri-therapy; avelumab; axitinib; palbociclib; dual matched normal and tumor biopsies; SIMS algorithm; Sequencing; Gene expression

Outcome Measures

Primary Outcomes (6)

• Incidence of the Tested 3-Drug Combination Therapy-Emergent Adverse Events and Serious Adverse Events

  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.

  From informed consent signature through 90 days after administration of the treatment (last dose)

• Response Rate (RR)

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

  Baseline up to approximately 24 months

• Duration of the Response

  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.

  Baseline up to approximately 24 months

• Progression-Free Survival (PFS)

  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.

  Baseline up to approximately 24 months

• Overall Survival (OS)

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

  Baseline up to approximately 24 months

• SIMS Algorithm to Predict Clinical Outcome

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

  4 years

Secondary Outcomes (2)

• Incidence of Treatment-related and or Biopsy-related Serious Adverse Events

  4 years

• Genomic and Transcriptomic Profile

  4 years

Study Arms (1)

Avelumab, Axitinib, Palbociclib

EXPERIMENTAL

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.

Drug: Avelumab; Drug: Axitinib; Drug: Palbociclib

Interventions

Avelumab DRUG

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

Avelumab, Axitinib, Palbociclib

Axitinib DRUG

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.

Also known as: Inlyta

Avelumab, Axitinib, Palbociclib

Palbociclib DRUG

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.

Also known as: Ibrance

Avelumab, Axitinib, Palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patients with documented oncogenic aberrations at enrollment: EGFR, ALK, ROS1 when available, MET exon 14 skipping when available. For squamous undifferentiated cell carcinoma, documentation of these aberrations is not mandatory. Note: For Phase 1 portion, all patients with adenocarcinoma histology must have documentation of results for druggable oncogenic aberrations (EGFR mutations, ALK rearrangements, and ROS1 when available) prior to enrollment on the study.
• For Phase 1 portion, \>2 lines of prior therapy in the metastatic setting.
• For the dose escalation phase of the study or until the MTD for the combination regimen has been determined, patients with moderate hepatic impairment defined as AST, ALT, alkaline phosphatase (ALP) \>5 times ULN, which would be grade 3 or higher. However, patients with liver metastases with AST/ALT ≤ 5 x ULN can be included in the study.
• For Phase 2 portion, any prior therapy in the metastatic setting.
• Clinical criteria for phase 1 and phase 2 studies:
• Patients with treated brain metastases are eligible as are patients with new, active untreated brain metastasis.
• Participants with a history of myocardial infarction within the last 2 years or with significant cardiac arrhythmias uncontrolled by medication or pacemaker,
• Participants with any history of interstitial lung disease,
• Prior clinically significant toxicities from anticancer agents or radiotherapy which have not regressed to Grade ≤ 1 severity (NCI-CTCAE version 4.03) apart from peripheral neuropathy and alopecia,
• History of any second malignancy in the last two years; patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease-free for at least two years,
• Autoimmune condition requiring medical intervention,
• Uncontrolled concomitant illness, active infection requiring i.v. antibiotics,
• Patients who have had a thromboembolic event within six months are excluded, as are patients on anticoagulants, except for low dose aspirin (\<100 mg/day) and low doses of anticoagulants meant to keep line access open;
• Patients with Grade 3 or 4 (serious) gastrointestinal bleeding within the last six months are excluded.
• Prior \> G3 hemoptysis, major blood vessel involvement (specifically including aorta, superior and inferior vena cave, main pulmonary arteries and veins, subclavian arteries and veins and other large blood vessels that in the investigator's opinion places the patients at high risk for major bleeding), and/or central cavitations,

Sponsors & Collaborators

• Worldwide Innovative Network Association: lead
• ARC Foundation for Cancer Research: collaborator
• Pfizer: collaborator

Study Sites (5)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

Avera Cancer Center

Sioux Falls, South Dakota, 57105, United States

Location

Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Centre Hospitalier Luxembourg

Luxembourg, 1210, Luxembourg

Location

Vall Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

Related Publications (1)

• Solomon B, Callejo A, Bar J, Berchem G, Bazhenova L, Saintigny P, Wunder F, Raynaud J, Girard N, Lee JJ, Sulaiman R, Prouse B, Bresson C, Ventura H, Magidi S, Rubin E, Young B, Onn A, Leyland-Jones B, Schilsky RL, Lazar V, Felip E, Kurzrock R. A WIN Consortium phase I study exploring avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer. Cancer Med. 2022 Jul;11(14):2790-2800. doi: 10.1002/cam4.4635. Epub 2022 Mar 20.

  PMID: 35307972 DERIVED

Related Links

• sponsor website
• SIMS article link: A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer.
• Link to the publication of the results of the Phase 1 part of the study

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab; Axitinib; palbociclib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

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.

Results Point of Contact

• Title: Fanny Wunder, Project Manager
• Organization: Worldwide Innovative Network (WIN) Association

fanny.wunder@winconsortium.org

0033604090029

Study Officials

• RAZELLE KURZROCK, MD

  Medical College of Wisconsin, Milwaukee, WI, USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2017
• First Posted: December 29, 2017
• Study Start: November 29, 2017
• Primary Completion: December 29, 2022
• Study Completion: December 29, 2022
• Last Updated: December 18, 2023
• Results First Posted: December 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); IL (1); ES (1); LU (1)