Cisplatin (CIS) Administered As Dry Powder for Inhalation (DPI) in Patients with Stage IV Non-Small Cell Lung Cancer

NCT06896890 | Recruiting Phase 1 DMC

• 1 other identifier: CIS-DPI-01
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 15

Brief Summary

The combination of chemotherapy and immunotherapy shows promising results in terms of overall survival (OS) and progression-free survival (PFS) for the treatment of first-line stage IV non-small cell lung cancer (NSCLC) patients, leading to such combinations becoming a real backbone of the Standard of Care (SoC) for NSCLC patients. However, conventional chemotherapy's severe systemic toxicities represent a limiting factor in terms of administered dose and frequency. Administration of cisplatin by inhalation (pulmonary route) is a promising additional approach that may overcome the limitations of conventional chemotherapy. Use of a dry powder inhaler enables a high therapeutic response by delivering high local concentrations of a well-established active substance without the usual undesired reactions that limit the use of high doses when administered through the conventional systemic route. This study may provide insights into whether this add-on treatment might be a safe and potentially efficacious option for NSCLC patients.

Conditions

NSCLC (advanced Non-small Cell Lung Cancer); Stage IV Lung Cancer

Keywords

non-small cell lung cancer; NSCLC; cisplatin; inhaled; pulmonary administration route; CIS-DPI; Dry Powder for Inhalation; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (dose escalation phase)

  Define the Maximum Tolerated Dose (MTD) based on Dose Limiting Toxicity (DLT). Dose-Limiting toxicity is defined to be a toxicity (i.e. confirmed investigational product related AE) that prevents further administration of the agent at that dose level.

  From first study treatment administration (Day 1) to the end of Week 12.

• Recommended Phase II dose (Safety expansion phase)

  Confirm the recommended phase II dose (RP2D) based on Dose Limiting Toxicity (DLT). Dose-Limiting toxicity is defined to be a toxicity (i.e. confirmed investigational product related AE) that prevents further administration of the agent at that dose level.

  From the first study treatment administration (Day 1) to the end of Week 12.

Secondary Outcomes (7)

• Pharmacodynamic markers

  From first study treatment administration (Day 1) to the end of Week 12.

• CIS-DPI efficacy - Objective response rate (ORR)

  From first study treatment administration (Day 1) to the end of Week 12.

• CIS-DPI efficacy - DCR

  From first study treatment administration (Day 1) to the end of Week 12.

• CIS-DPI efficacy - BOR

  From first study treatment administration (Day 1) to the end of Week 12.

• CIS-DPI efficacy - DOR

  From first study treatment administration (Day 1) to the end of Week 12.

Other Outcomes (18)

• CIS-DPI induced Immune Reactions

  From first study treatment administration (Day 1) to the end of Week 12.

• CIS-DPI induced Immune Reactions

  From first study treatment administration (Day 1) to the end of Week 12.

• CIS-DPI efficacy - RECIST 1.1 Tumor burden

  From first study treatment administration (Day 1) to the end of Week 12.

Study Arms (1)

Cisplatin Dry Powder for Inhalation (CIS-DPI)

EXPERIMENTAL

Stage IV NSCLC patients with Programmed Death-Ligand Tumor Propensity Score (PDL1 TPS) ≥50% OR \<50%, respectively receiving study treatment CIS-DPI combined with standard of care treatment (either iv pembrolizumab OR iv pembrolizumab and iv carboplatin-doublet chemotherapy (i.e. pemetrexed + carboplatin in non-squamous NSCLC patients or paclitaxel + carboplatin in squamous NSCLC patients)).

Drug: CIS-DPI

Interventions

CIS-DPI DRUG

* Administration of cisplatin by inhalation (pulmonary route) using single-use RS01 capsule-based device and CIS-DPI hard capsules containing 2.5 mg, 5 mg, and 10 mg cisplatin. * CIS-DPI, administered once-a-day, 5-days on followed by 2-days off. Daily dose to be administered will range from an initial dose of 2.5 mg cisplatin to a maximal theoretical dose of 30 mg (i.e., dose 1 to dose 7).

Also known as: Cisplatin-based Dry Powder for Inhalation

Cisplatin Dry Powder for Inhalation (CIS-DPI)

Eligibility Criteria

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

You may qualify if:

• The patient must be ≥18 years of age at the time of signing the informed concent form (ICF).
• The patient must have a pathologically or cytologically confirmed Stage IV NSCLC that could be treated with pembrolizumab alone or combined with carboplatin/pemetrexed or paclitaxel.
• The patient must have measurable disease according to RECIST 1.1.
• The patient must be treatment naïve for stage IV NSCLC at the time of study enrolment. Patients having received, at least 6 months before D1, platinum derivatives adjuvant after (i) surgery or (ii) concomitant chemotherapy-radiotherapy for unresectable locally advanced NSCLC are eligible.
• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• The patient must have adequate organ function values as follows:
• Haematology:
• Platelet count \>100,000 cells/mm3.
• Absolute neutrophil count \>1,500 cells/mm3.
• Haemoglobin \>9 g/dL.
• Serum creatinine less or equal to upper limit of normal (ULN) or creatinine clearance \>60 mL/min/1.73 m2 on the basis of Cockcroft-Gault glomerular filtration rate estimation.
• Coagulation:
• International normalised ratio (INR) ≤1.5; for patients treated with coumarins INR ≤3 is acceptable.
• Prothrombin time (PTtest) and activated partial thromboplastin time (aPTT) \<1.6 x ULN unless therapeutically warranted.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3 x ULN. In case of hepatic metastasis, AST and ALT \<5 x ULN.

You may not qualify if:

• Patients with contraindication to or unwillingness to undergo contrast-enhanced computed tomography (CT) scans and chest X-rays according to the protocol requirements.
• Patients who are participating in an investigational drug or device study within 4 weeks prior to the planned day for the first study treatment administration (D1).
• Patients who have been treated by any anti-neoplastic agent within 6 months prior to the planned day for the first study treatment administration (D1).
• Patients who have received prior therapy with an immune checkpoint inhibitor.
• Patients who have received prior radiotherapy (head, neck, thorax, or abdomen) within 4 weeks prior to the planned day for the first study treatment administration (D1) except palliative radiotherapy (2 weeks). Patients must have recovered from all radiation-related toxicities, not require corticosteroids (see criterion 2425) and not have had radiation pneumonitis \>grade 2.
• Patients with concurrent thoracic irradiation for the treatment of lung cancer.
• Patients who underwent major surgery within 4 weeks before the planned day for the first study treatment administration (D1).
• Non-smoking patients without results of Epidermal growth factor receptor (EGFR) mutation and anaplastic large-cell lymphoma kinase (ALK) translocation before the planned day for the first study treatment administration (D1).
• Patients with known pre-existing hearing impairment due to VIII nerve alteration.
• Patients presenting a history of previous severe intolerance to or sensitivity to cisplatin, vitamin E or lactose.
• Patients with mouth problems (e.g. cleft palate) or other abnormalities that would prevent tight fit of the mouth seal.
• Patients with uncontrolled symptomatic pleural effusion or uncontrolled pneumothorax.
• Patients having undergone pneumonectomy or bilobectomy (except if bilobectomy includes the right middle lobe).
• Patients with a known history of severe cough/bronchospasm upon inhalation of dry powder inhalation products.
• Patients with a known history or current evidence of any chronic upper or lower respiratory conditions (other than asthma and allergic or non-allergic rhinitis). History of mild acute upper or lower respiratory conditions are allowed, provided that the condition has been resolved at least 3 months before the planned day for the first study treatment administration (D1) and provided that, in the investigator's judgement, this occurrence poses no additional risk for this subject.

Sponsors & Collaborators

• Inhatarget Therapeutics: lead

Study Sites (15)

Institut Jules Bordet - Hôpital Universitaire de Bruxelles

Brussels, Belgium

RECRUITING

GHDC

Charleroi, Belgium

RECRUITING

CHU Helora - Site Jolimont

Jolimont, Belgium

RECRUITING

AZ Groeninge

Kortrijk, Belgium

RECRUITING

CHU Sart Tilman

Liège, Belgium

RECRUITING

CHU Ambroise Paré

Mons, Belgium

RECRUITING

AZ Delta

Roeselare, Belgium

RECRUITING

Université Paris-Saclay, UVSQ, APHP - Hôpital Ambroise Paré

Boulogne-Billancourt, France

NOT YET RECRUITING

Centre François Baclesse de Caen

Caen, France

NOT YET RECRUITING

Hôpital Européen Georges Pompidou, Paris-Cite University

Paris, France

NOT YET RECRUITING

L'Institut de Cancérologie de l'Ouest

Saint-Herblain, France

NOT YET RECRUITING

Instituto Oncologico Dr Rosell, Hospital Universitario Dexeus

Barcelona, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Universitario La PAZ, IdiPAZ

Madrid, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Spain

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Respiratory Aspiration

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Thierry Berghmans, Prof.MD.

  Hopital Universitaire de Bruxelles (HUB)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédéric De Coninck

CONTACT

+32 (0) 484 71 37 73; frederic.de.coninck@inhatarget.com

Wendy Sonnet, MSc, PhD

CONTACT

wendy.sonnet@inhatarget.com

Study Design

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

Model Details: A Phase I/II First-in-Human Single-arm Open-label Multicentre Clinical Trial

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 26, 2025
• Study Start: June 23, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

FR (4); BE (7); ES (4)