Phase II umbrella study of novel anti-cancer agents in patients with NSCLC who progressed on an anti-PD-1/PD-L1 containing therapy - HUDSON

Study identifier:D6185C00001

ClinicalTrials.gov identifier:NCT03334617

EudraCT identifier:2017-002208-28

CTIS identifier:N/A

Recruiting

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).

Medical condition

Non-small Cell Lung Cancer

Phase

Phase 2

Healthy volunteers

Study drug

Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, AZD9150, AZD6738, Vistusertib, Olaparib, Oleclumab, trastuzumab deruxtecan, cediranib, AZD6738 (ceralasertib), AZD6738 (ceralasertib), AZD6738 (ceralasertib) (240 mg or 160 mg), AZD6738 (ceralasertib) 7 days monotherapy

Sex

All

Actual enrollment

570

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 18 Dec 2017

Estimated Primary Completion Date: 27 Feb 2025

Estimated Study Completion Date: 27 Feb 2025

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 May 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

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-Β ligand (RANKL) inhibitors for the treatment of bone metastases.
-history of active primary immunodeficiency

Sort by status

No locations available

Arms	Assigned Interventions
Experimental: Durvalumab + olaparib Durvalumab given in combination with olaparib .	Drug: Durvalumab Durvalumab given IV at 1500 mg Q4W ±2 days Drug: Olaparib Olaparib (AZD2281) given orally at 300 mg BD
Experimental: Durvalumab + AZD9150 Durvalumab given in combination with AZD9150.	Drug: Durvalumab Durvalumab given IV at 1500 mg Q4W ±2 days Drug: AZD9150 AZD9150 given IV at 200mg every other day of a 1-week lead-in period followed by QW
Experimental: Durvalumab + AZD6738 Durvalumab given in combination with AZD6738.	Drug: Durvalumab Durvalumab given IV at 1500 mg Q4W ±2 days Drug: 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
Experimental: Durvalumab + vistusertib Durvalumab given in combination with Vistusertib (AZD2014).	Drug: Durvalumab Durvalumab given IV at 1500 mg Q4W ±2 days Drug: Vistusertib Vistusertib (AZD2014) given orally at a dose of 125 mg BD on an intermittent dosing schedule of 2 days on, 5 days off
Experimental: Durvalumab + Oleclumab Durvalumab given in combination with Oleclumab	Drug: Durvalumab Durvalumab given IV at 1500 mg Q4W ±2 days Drug: Oleclumab Oleclumab given at dose level 1 for 2 cycles and then dose level 2 thereafter
Experimental: durvalumab + trastuzumab deruxtecan durvalumab given in combination with trastuzumab deruxtecan (DS-8201a)	Drug: 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
Experimental: durvalumab + cediranib durvalumab given in combination with cediranib (AZD2171)	Drug: Durvalumab Durvalumab given IV at 1500 mg Q4W ±2 days Drug: cediranib cediranib given orally at 20 mg tablets on an intermittent schedule (5 days on, 2 days off), starting on C1D1
Experimental: AZD6738 (ceralasertib) monotherapy AZD6738 (ceralasertib) given as monotherapy	Drug: AZD6738 (ceralasertib) AZD6738 given at 240 mg twice daily for 14 days on treatment in each 28-day cycle, between Days 1 and 14.
Experimental: durvalumab & AZD6738 (ceralasertib) durvalumab given in combination with AZD6738 (D15-D28)	Drug: Durvalumab Durvalumab given IV at 1500 mg Q4W ±2 days Drug: 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
Experimental: durvalumab & AZD6738 (ceralasertib) (240 mg or 160 mg) durvalumab in combination with twice daily 160 mg or 240 mg AZD6738 (D22-D28)	Drug: 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
Experimental: AZD6738 (ceralasertib) 7 days monotherapy AZD6738 (ceralasertib) monotherapy on D1-7 of every 28 days	Drug: 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

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

John Heymach

The University of Texas MD Anderson Cancer Center