Ireland
--:--IST
Latest
Active, not recruiting Phase 2

Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy

NCT03334617 · tracked via the Priya Life Science Canada tracker
Phase
Phase 2
Started
2017-12-18
Last updated
2025-10-27

Condition(s) studied

Non-Small Cell Lung Cancer

Investigational drug(s) / intervention(s)

Durvalumab →Danvatirsen →Ceralasertib →Vistusertib →Olaparib →Oleclumab →Trastuzumab deruxtecan →Cediranib →

Durvalumab: Participants will receive IV infusion of durvalumab as stated in arm description.

Danvatirsen: Participants will receive IV infusion of danvatirsen as stated in arm description.

Ceralasertib: Participants will receive oral tablet of ceralasertib as stated in arm description.

Vistusertib: Participants will receive oral tablets of vistusertib as stated in arm description.

Olaparib: Participants will receive oral tablets of olaparib as stated in arm description.

Oleclumab: Participants will receive IV infusion of oleclumab as stated in arm description.

Trastuzumab deruxtecan: Participants will receive IV infusion of trastuzumab deruxtecan as stated in arm description.

Cediranib: Participants will receive oral tablets of cediranib as stated in arm description.

Study summary

This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.

Eligibility

Sex
ALL
Min age
18 Years
Max age
99 Years
Healthy volunteers
No
Inclusion criteria: * At least 18 years of age at the time of signing the informed consent form. * Participant must have histologically or cytologically confirmed metastatic or locally advanced and recurrent non-small-cell lung cancer (NSCLC) which is progressing. * Participants eligible for second- or later-line therapy, who must have received an anti-programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) containing therapy and a platinum-doublet regimen for locally advanced or metastatic NSCLC either separately or in combination. Prior durvalumab is acceptable. The participant must have had disease progression on a prior line of anti-PD-1/PD-L1 therapy. * Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) performance status of 0 to 1, and a minimum life expectancy of 12 weeks. * Participant must have at least 1 lesion that can be accurately measured. A previously irradiated lesion can be considered a target lesion if the lesion has clearly progressed. * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants. Exclusion Criteria: * Participants whose tumour samples have targetable alterations in epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) at initial diagnosis are excluded. In addition, participants whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded. * Active or prior documented autoimmune or inflammatory disorders. * Active infection including tuberculosis, hepatitis B (known positive hepatitis B virus \[HBV\] surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus (positive human immunodeficiency virus \[HIV\] 1/2 antibodies). * Female participant who are pregnant or breastfeeding, or male or female participants of reproductive potential who are not willing to employ effective birth control. * Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients, or history of severe hypersensitivity reactions to other monoclonal antibodies. * Participant has spinal cord compression or symptomatic brain metastases. * Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Participants may receive treatment with bisphosphonates or receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors for the treatment of bone metastases. * History of active primary immunodeficiency.

Primary outcome measure(s)

  • Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) — Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)
    Objective response was defined as participants with a confirmed investigator-assessed response complete response (CR) or partial response (PR) based on RECIST v 1.1. The CR is defined as disappearance of all target (TL) and non-target lesions (NTL), and any pathological lymph node (whether target or nontarget) must have reduction in short axis to \<10 mm. The PR is defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum diameters, as long as criteria for progressive disease (PD) are not met. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from date of first documentation. Percentage of participants with objective response was reported.

Trial sites (45)

FacilityCityRegionStatus
Research Site Duarte California
Research Site Fullerton California
Research Site La Jolla California
Research Site Los Angeles California
Research Site Washington D.C. District of Columbia
Research Site Chicago Illinois
Research Site Baltimore Maryland
Research Site Baltimore Maryland
Research Site Boston Massachusetts
Research Site St Louis Missouri
Research Site New York New York
Research Site Philadelphia Pennsylvania
Research Site Pittsburgh Pennsylvania
Research Site Nashville Tennessee
Research Site Nashville Tennessee
Research Site Houston Texas
Research Site Fairfax Virginia
Research Site Innsbruck Austria
Research Site Salzburg Austria
Research Site Vienna Austria
Research Site Vienna Austria
Research Site Edmonton Alberta
Research Site Brampton Ontario
Research Site Ottawa Ontario
Research Site Toronto Ontario
Research Site Montreal Quebec
Research Site Bordeaux France
Research Site Nantes France
Research Site Paris France
Research Site Villejuif France
Research Site Berlin Germany
Research Site Esslingen a.N. Germany
Research Site Großhansdorf Germany
Research Site Heidelberg Germany
Research Site Haifa Israel
Research Site Kfar Saba Israel
Research Site Petah Tikva Israel
Research Site Ramat Gan Israel
Research Site Seoul South Korea
Research Site Seoul South Korea

+ 5 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03334617 on ClinicalTrials.gov ↗ ← All trials in Canada