Predicting Response to Neoadjuvant ATEZOLIZUMAB Plus Carboplatin/Nab Paclitaxel in Resectable Non-squamous NSCLC

NCT04865250 | Recruiting Phase 2 DMC

• 1 other identifier: iReP
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Exploratory study evaluating the potential of immune signature profiling for predicting response in patients with resectable Stage II, IIIA and select IIIB (T3N2 only) non-squamous Non-Small Cell Lung Cancer (NSCLC) to neoadjuvant ATEZOLIZUMAB plus Carboplatin/nab Paclitaxel Atezolizumab is given as intravenous infusion at a fixed dose of 1200 mg, day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase, Carboplatin at an initial dose of AUC (area under curve) 5 mg/mL/min, intravenously day 1 of each 21-day cycle for 3 cycles during the neoadjuvant treatment Phase, and Nab-Paclitaxel (Abraxane) at 100 mg/m2, intravenously day 1, 8 and 15 of each 21-day cycle for 3 cycles during the neoadjuvant treatment phase. Surgery after the 3rd cycle Atezolizumab / Carboplatin / Nab-Paclitaxel is standard procedure.

Conditions

NSCLC Stage II; NSCLC, Stage IIIA; NSCLC Stage IIIB

Outcome Measures

Primary Outcomes (1)

• Response to neoadjuvant immunochemotherapy with ATEZOLIZUMAB, Carboplatin and nab-Paclitaxel

  determined by Major Pathologic Response (MPR) (≤10% residual viable tumor cells) (pathologic regression grading according to Junker criteria) rate

  up to 5 months (after 9 weeks of neoadjuvant immunochemotherapy (3 cycles with 21 days per cycle) + surgery (4-8 additional weeks after completion of neoadjuvant immunochemotherapy)

Secondary Outcomes (5)

• Response rate according to RECIST 1.1 criteria

  pre-surgery after completion of neoadjuvant immunochemotherapy

• Response rate as determined by Δ PETactivity

  pre-surgery after completion of neoadjuvant immunochemotherapy

• Event-free survival (EFS)

  up to 29 months after study inclusion; calculated from start of 1st cycle of neoadjuvant treatment, thus including three 21 day cycles+surgery, follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery

• Overall survival (OS)

  up to 29 months after study inclusion; calculated from start of 1st cycle of neoadjuvant treatment, thus including three 21 day cycles+surgery, follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery

• Number of patients attaining surgery as planned

  up to 5 months

Study Arms (1)

treatment

EXPERIMENTAL

ATEZOLIZUMAB; Carboplatin; Nab-Paclitaxel

Drug: Atezolizumab 1200 mg abs day 1 q22 (iv)

Interventions

Atezolizumab 1200 mg abs day 1 q22 (iv) DRUG

Immune checkpoint blockade antibody ATEZOLIZUMAB directed against PD-L1 (Programmed death-ligand 1); Carboplatin; Nab-Paclitaxel (iv)

Also known as: Carboplatin AUC5 day 1 q22 (iv), Nab-Paclitaxel 100 mg/m2 day 1,8,15 q22

treatment

Eligibility Criteria

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

You may qualify if:

• Informed consent, patients age ≥ 18-year-old including, signed and dated
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Histologically confirmed NSCLC of non-squamous histology, cStage II, IIIA or select IIIB (T3N2 only); for T-status ≤ T3 allowed; for N2 patients only IIIa1-3 Robinson classification allowed
• Deemed surgically resectable with curative intent by an attending thoracic surgeon after adequate staging including PET-CT (positron emission tomography)
• Adequate lung and cardiac function for intended lung resection according to German S3 regulation
• Radiologically measurable disease as defined by response evaluation criteria in solid tumors RECIST v1.1
• Sufficient availability of the tissue sample from primary tumor before start of neoadjuvant treatment
• Females of child-bearing potential must agree to use, and be able to comply with, effective contraception (\</=1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 120 days after the last dose of study medication
• Females must have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
• Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following treatment discontinuation, even if he has undergone a successful vasectomy.
• adequate renal, hepatic, and bone marrow function as defined below
• Absolute neutrophil count (ANC) \> 1500/μl
• Platelet count ≥ 100000/μl
• Hemoglobin ≥ 9 g/dl (can be post-transfusion)
• International normalized ratio (INR) ≤ 1.4 in patients not receiving anticoagulation; for patients receiving respective anticoagulation an INR ≤3.0 allowed

You may not qualify if:

• Illness or condition that may interfere with a patient's capacity to understand, follow, and/or comply with study procedures
• Treatment in any other clinical trial within 30 days before screening.
• NSCLC Stage cT4
• NSCLC stage cN3 or cN2 IIIA4 (bulky or fixed multi-station N2 disease) according to Robinson classification
• NSCLC of squamous cell histology
• Any prior therapy for lung cancer (including systemic therapy, radiotherapy or major surgery)
• History of allogeneic tissue / solid organ transplant or allogeneic stem cell transplantation
• Patients with active hepatitis B or C infections or a history of HIV infection
• Pregnant or lactating women
• Active autoimmune disease or history of severe autoimmune disease or immunodeficiency or a syndrome that requires systemic steroids or immunosuppressive agents
• The following exceptions are granted:
• patients with vitiligo, eczema, lichen simplex or resolved childhood asthma/atopy
• subjects requiring intermittent use of bronchodilatators or local steroid injections
• patients with hypothyroidism stable on hormone replacement
• Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to Cycle 1, Day 1 (except low-dose steroids for adrenal failure or emesis prophylaxis)

Sponsors & Collaborators

• University Hospital Heidelberg: lead
• Dietmar Hopp Stiftung: collaborator

Study Sites (1)

Thoraxklinik Heidelberg gGmbH

Heidelberg, BaWü, 69126, Germany

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Dirk Jäger, Prof. med.

CONTACT

+49 6221 56 7229; Dirk.Jaeger@med.uni-heidelberg.de

Martin Eichhorn, PD Dr. med.

CONTACT

+496221 396 1101; Martin.Eichhorn@med.uni-heidelberg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr. med.

Model Details: Exploratory, open-label, non-randomized, single treatment, phase II study

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: April 29, 2021
• Study Start: January 7, 2021
• Primary Completion: November 30, 2024
• Study Completion (Estimated): December 30, 2026
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)