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

Recruitment Complete

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

Sex

All

Actual Enrollment

531

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 18 Dec 2017

Estimated Primary Completion Date: 04 Sept 2024

Estimated Study Completion Date: 04 Sept 2024

Study design

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

Verification:

Verified 01 Dec 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

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