Her2-positive Lung Cancer Treated With Dedicated Drug

NCT03845270 | Completed Phase 2

• 1 other identifier: IFCT-1703
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 18

Brief Summary

HER2 (erbB-2/neu) is a member of the erbB receptor tyrosine kinase family. ERBB2 gene which encodes human epidermal growth factor 2 (HER2) is a major proliferative driver activating downstream signaling through PI3K-AKT and MEK-ERK. HER2 overexpression or gene amplification is associated with sensitivity to trastuzumab and lapatinib in breast cancer. Among actual lung cancer biomarker, HER2 remains apart. HER2 involvement is known for a long time but clinical research has been stopped for many years since the first clinical trials in unselected patients were negative. Recently trastuzumab + pertuzumab + docetaxel has been tested for first-line treatment of HER2-positive metastatic breast cancer (CLEOPATRA trial). Analysis of the primary end point showed that patients who received pertuzumab, trastuzumab, and docetaxel (pertuzumab group) had a significantly longer median progression-free survival, as assessed by independent reviewers an did those who received placebo, trastuzumab, and docetaxel (control group) (hazard ratio favoring the pertuzumab group, 0.62). There is thus a strong rational for treating HER2 mutated lung cancer patient with these drugs.

Conditions

Non Small Cell Lung Cancer Metastatic; Non Small Cell Lung Cancer Stage III; HER2 Gene Mutation

Keywords

IFCT; NSCLC; HER2

Outcome Measures

Primary Outcomes (1)

• Overall Response

  Proportion of patients with a confirmed complete response or partial response according to RECIST version 1.1

  [Time Frame: About 24 months]

Secondary Outcomes (6)

• Objective Response Rate

  6 weeks

• Overall Survival

  About 24 months

• Progression-free survival

  About 24 months

• Duration of response

  About 24 months

• Objective Response Rate

  6 weeks (confirmation needed at least after 4 weeks)

Other Outcomes (1)

• Correlation between OR, PFS, and HER2 mutation kinetic on cfDNA

  About 24 months

Study Arms (1)

pertuzumab + trastuzumab + docetaxel

EXPERIMENTAL

Cycle 1 : D1 : pertuzumab 840 mg, D2 : trastuzumab 8 mg/kg + docetaxel 75 mg/m² Subsequent cycle : D1 : pertuzumab 420 mg + trastuzumab 6 mg/kg + docetaxel 75 mg/m²

Drug: pertuzumab + trastuzumab + docetaxel

Interventions

pertuzumab + trastuzumab + docetaxel DRUG

Cycle 1 : D1 : pertuzumab 840 mg, D2 : trastuzumab 8 mg/kg + docetaxel 75 mg/m² Subsequent cycle : D1 : pertuzumab 420 mg + trastuzumab 6 mg/kg + docetaxel 75 mg/m²

pertuzumab + trastuzumab + docetaxel

Eligibility Criteria

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

You may qualify if:

• Patient having signed an informed consent form
• Histologically or cytologically confirmed NSCLC (per 2015 8th edition TNM classification)
• Not suitable for radiation, inoperable stage III or stage IV
• HER2 exon 20 mutation or insertion among which: in-frame insertions in exon 20 between codons 775 and 881 including the 12bp insertion with a duplication / insertion of 4 amino acids (YVMA) at codon 775, the 3bp insertion with a complex insertion-substitution G776\>VC and point mutations L755S and G776C. Other mutation/insertion should be discussed with IFCT. Analysis must be performed in INCa-labelled laboratories or platforms according to a validated procedure.
• Prior treatment with at least one regimen of platinum-based chemotherapy with documented disease progression.
• Note: taxanes are allowed provided that no grade \>2 associated adverse event occurred (except hematological toxicity).
• Presence of at least one lesion that can be measured by CT scan (RECIST v1.1)
• Age ≥ 18 years
• Adequate organ function, as evidenced by the following laboratory results:
• ANC \> 1500 cells/mm3 Platelet count \> 100,000 cells/mm3 Hemoglobin \> 9.0 g/dL Patients are allowed to receive transfused RBC to achieve this level. Total bilirubin ≤ 1.5 × ULN, except in patients with previously documented Gilbert's syndrome, in which case the direct bilirubin should be less than or equal to the ULN SGOT and SGPT ≤ 2.5 × ULN Alkaline phosphatase ≤ 2.5 × ULN, Alkaline phosphatase \< 5×ULN and SGOT and SGPT \< 5×ULN for patients with hepatic and/or bone metastases Clearance creatinine ≥ 30 mL/min INR and aPTT ≤ 1.5 x ULN This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
• WHO performance index of 0, 1 or 2
• LVEF ≥ 50%
• Patient who is capable, according to the investigator, of complying with the study's requirements and restrictions
• Estimated life expectancy \> 3 months
• A female is eligible to enter and participate in this study if she is of:

You may not qualify if:

• History of cancer except cancer dating from over two years ago and considered to be cured, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma and stage I uterine cancer.
• Any approved anti-cancer therapy ≤ 21 days before enrollment. Note: TKIs approved for the treatment of NSCLC must be discontinued ≥ 7 days prior to the first study treatment on Cycle 1, Day 1. (The baseline scan must be completed after discontinuation of TKIs).
• Patients with concomitant EGFR, ALK, ROS1, MET, BRAF and KRAS mutation. Other molecular co-alterations should be discussed with IFCT before patient's enrollment.
• Previous treatment with an anti-HER2 agent.
• Previous irradiation \<14 days before enrollment.
• Brain metastases that are symptomatic, or require any radiation, surgery, or corticosteroid therapy to control symptoms from brain metastases within 4 weeks before enrollment. Asymptomatic brain metastases with a fixed dose of steroids for at least 2 weeks are eligible.
• Carcinomatous meningitis
• History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab, pertuzumab or docetaxel or murine proteins or one of the excipients
• Pregnancy and breast-feeding
• Any evidence of severe or uncontrolled systemic disease. (E.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) or other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study.
• Evidence of active pneumonitis during screening
• Current unstable ventricular arrhythmia requiring treatment, history of symptomatic congestive heart failure (CHF; New York Heart Association \[NYHA\] Classes II-IV) and history of myocardial infarction or unstable angina within 6 months before enrollment.
• Unresolved toxicity grade \> 2 from previous anti-tumor treatments

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead

Study Sites (18)

CHU Besançon

Besançon, France

Location

CHU de Bordeaux

Bordeaux, France

Location

Caen - CHU Côte de Nacre

Caen, 14000, France

Location

Clermont-Ferrand - CHU

Clermont-Ferrand, France

Location

CHI Créteil

Créteil, France

Location

CHRU Grenoble

Grenoble, France

Location

Centre Hospitalier - Pneumologie

Le Mans, 72000, France

Location

Lyon - URCOT

Lyon, France

Location

Hôpital Nord APHM

Marseille, France

Location

Montpellier - CHRU

Montpellier, 34295, France

Location

CHU de Nantes

Nantes, France

Location

Nice CLCC

Nice, France

Location

AP-HP Hopital Tenon - Pneumologie

Paris, 75020, France

Location

AP-HP Hôpital Bichat

Paris, France

Location

Rennes - CHU

Rennes, 35033, France

Location

CHU Strasbourg

Strasbourg, France

Location

CHU Toulouse

Toulouse, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Mazieres J, Lafitte C, Ricordel C, Greillier L, Negre E, Zalcman G, Domblides C, Madelaine J, Bennouna J, Mascaux C, Moro-Sibilot D, Pinquie F, Cortot AB, Otto J, Cadranel J, Langlais A, Morin F, Westeel V, Besse B. Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non-Small-Cell Lung Cancer Harboring HER2 Mutations: Results From the IFCT-1703 R2D2 Trial. J Clin Oncol. 2022 Mar 1;40(7):719-728. doi: 10.1200/JCO.21.01455. Epub 2022 Jan 24.

  PMID: 35073148 RESULT

Related Links

• IFCT website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pertuzumab; Trastuzumab; Docetaxel

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 19, 2019
• Study Start: May 17, 2019
• Primary Completion: February 1, 2021
• Study Completion: December 18, 2023
• Last Updated: December 19, 2023

Record last verified: 2023-12

Locations

FR (18)