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

Non-Small Cell Lung Cancer Clinical Trial

— HUDSON  

Official title:

An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients With Non-Small Cell Lung Cancer, Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03334617
• Other study ID #: D6185C00001
• Secondary ID: 1380502023-50900
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 18, 2017
• Est. completion date: September 4, 2024

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multi-centre, umbrella Phase II study in patients 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.

Description:

This is an open-label, multi-centre, umbrella Phase II study in patients with metastatic non-small cell lung cancer (NSCLC) who have progressed on an anti-programmed cell death-1/anti-programmed cell death ligand 1 (anti-PD-1/PD-L1) containing therapy. This study is modular in design, consisting of a number of treatment cohorts, allowing evaluation of the efficacy, safety, and tolerability of multiple treatment arms. There is currently no established therapy for patients who have received immune checkpoint inhibitors and platinum-doublet therapies, and novel treatments are urgently needed.

This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 531
• Est. completion date: September 4, 2024
• Est. primary completion date: September 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion criteria:

• At least 18 years of age at the time of signing the informed consent form.

• Patient must have histologically or cytologically confirmed metastatic or locally advanced and recurrent NSCLC which is progressing.

• Patients eligible for second- or later-line therapy, who must have received an antiPD1/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 patient must have had disease progression on a prior line of antiPD1/PD-L1 therapy.

• ECOG/WHO performance status of 0 to 1, and a minimum life expectancy of 12 weeks.

• Patient 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 patients.

Exclusion Criteria:

• Patients whose tumour samples have targetable alterations in EGFR and/or ALK at initial diagnosis are excluded. In addition, patients 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 HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).

• Female patients who are pregnant or breastfeeding, or male or female patients 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.

• Patient has spinal cord compression or symptomatic brain metastases.

• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Patients may receive treatment with bisphosphonates or receptor activator of nuclear factor kappa-? ligand (RANKL) inhibitors for the treatment of bone metastases.

• history of active primary immunodeficiency

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Durvalumab
Durvalumab given IV at 1500 mg Q4W ±2 days
• AZD9150
AZD9150 given IV at 200mg every other day of a 1-week lead-in period followed by QW
• AZD6738
AZD6738 given orally at 240mg twice daily in Cycle 0 Days 1-7, followed by 7 days on treatment in each cycle between Days 22-28
• Vistusertib
Vistusertib (AZD2014) given orally at a dose of 125 mg BD on an intermittent dosing schedule of 2 days on, 5 days off
• Olaparib
Olaparib (AZD2281) given orally at 300 mg BD
• Oleclumab
Oleclumab given at dose level 1 for 2 cycles and then dose level 2 thereafter
• trastuzumab deruxtecan
Durvalumab given IV at 1120mg Q3W ±2 days for Module 6 only & trastuzumab deruxtecan given at 5.4 mg/kg via IV infusion Q3W ±2 days
• cediranib
cediranib given orally at 20 mg tablets on an intermittent schedule (5 days on, 2 days off), starting on C1D1
• AZD6738 (ceralasertib)
AZD6738 given at 240 mg twice daily for 14 days on treatment in each 28-day cycle, between Days 1 and 14.
• AZD6738 (ceralasertib)
AZD6738 given orally at 240mg twice daily for 14 days in each 28 day cycle (starting from Cycle 1) between Days 15-28
• AZD6738 (ceralasertib) (240 mg or 160 mg)
AZD6738 given orally at 240mg or 160mg twice daily in Cycle 0 Days 1-7, followed by 7 days on treatment in each cycle between Days 22-28
• AZD6738 (ceralasertib) 7 days monotherapy
AZD6738 given orally at 240 mg twice daily for 7 days on Day 1-7 in each 28 day cycle

Locations

Country	Name	City	State
Austria	Research Site	Innsbruck
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Austria	Research Site	Wien
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
France	Research Site	Bordeaux
France	Research Site	Nantes Cedex 1
France	Research Site	Paris
France	Research Site	Villejuif
Germany	Research Site	Berlin
Germany	Research Site	Esslingen a.N.
Germany	Research Site	Grosshansdorf
Germany	Research Site	Heidelberg
Germany	Research Site	Köln
Israel	Research Site	Haifa
Israel	Research Site	Kfar Saba
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	Duarte	California
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fullerton	California
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Los Angeles	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Israel,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events/serious adverse events to assess the safety and tolerability of each treatment	Physical examinations, laboratory findings, and vital signs AEs/SAEs collected throughout the study, from informed consent until the safety follow-up visit	Through to study completion, up to 3.5 years.
Primary	Assessment of the efficacy of each treatment by evaluation of objective response rate	Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1); Objective response rate (ORR)	12 weeks
Secondary	Disease control rate (DCR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.	Assessment of the anti-tumour activity of each therapy.	Through to study completion, up to 3.5 years.
Secondary	Best percentage change in tumour size using RECIST 1.1 assessment for the anti-tumour activity of each therapy	Assessment of the anti-tumour activity of each therapy.	Through to study completion, up to 3.5 years.
Secondary	Duration of response (DoR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.	Assessment of the anti-tumour activity of each therapy.	Through to study completion, up to 3.5 years
Secondary	Progression free survival (PFS) using RECIST 1.1 assessment for the anti-tumour activity of each therapy.	Assessment of the anti-tumour activity of each therapy.	Through to study completion, up to 3.5 years.
Secondary	Overall surival (OS)	Assessment of the anti-tumour activity of each therapy.	Through to study completion, up to 4.5 years.