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)

• ClinicalTrials.gov Identifier: NCT03334617
• Recruitment Status: Active, not recruiting
• First Posted: November 7, 2017
• Last Update Posted: March 15, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Non-Small Cell Lung Cancer	Drug: Durvalumab; Drug: AZD9150; Drug: AZD6738; Drug: Vistusertib; Drug: Olaparib; Drug: Oleclumab; Drug: trastuzumab deruxtecan; Drug: cediranib; Drug: AZD6738 (ceralasertib); Drug: AZD6738 (ceralasertib) (240 mg or 160 mg); Drug: AZD6738 (ceralasertib) 7 days monotherapy	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 531 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

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.

Within each module, there will be treatment cohorts.

• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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).
• Actual Study Start Date: December 18, 2017
• Estimated Primary Completion Date: September 4, 2024
• Estimated Study Completion Date: September 4, 2024

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Assessment of the efficacy of each treatment by evaluation of objective response rate [ Time Frame: 12 weeks ]

   Endpoint based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

   Objective response rate (ORR)

Secondary Outcome Measures :

1. Disease control rate (DCR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years. ]
   Assessment of the anti-tumour activity of each therapy.
2. Best percentage change in tumour size using RECIST 1.1 assessment for the anti-tumour activity of each therapy [ Time Frame: Through to study completion, up to 3.5 years. ]
   Assessment of the anti-tumour activity of each therapy.
3. Duration of response (DoR) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years ]
   Assessment of the anti-tumour activity of each therapy.
4. Progression free survival (PFS) using RECIST 1.1 assessment for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, up to 3.5 years. ]
   Assessment of the anti-tumour activity of each therapy.
5. Overall surival (OS) [ Time Frame: Through to study completion, up to 4.5 years. ]
   Assessment of the anti-tumour activity of each therapy.

Other Outcome Measures:

1. Incidence of adverse events/serious adverse events to assess the safety and tolerability of each treatment [ Time Frame: Through to study completion, up to 3.5 years. ]
   Physical examinations, laboratory findings, and vital signs AEs/SAEs collected throughout the study, from informed consent until the safety follow-up visit

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Research Site

Duarte, California, United States, 91010

Research Site

Fullerton, California, United States, 92835

Research Site

La Jolla, California, United States, 92093

Research Site

Los Angeles, California, United States, 90095

United States, District of Columbia

Research Site

Washington, District of Columbia, United States, 20016

United States, Illinois

Research Site

Chicago, Illinois, United States, 60637

United States, Maryland

Research Site

Baltimore, Maryland, United States, 21224

Research Site

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02215

United States, Missouri

Research Site

Saint Louis, Missouri, United States, 63110

United States, New York

Research Site

New York, New York, United States, 10032

United States, Pennsylvania

Research Site

Philadelphia, Pennsylvania, United States, 19111

Research Site

Pittsburgh, Pennsylvania, United States, 15232

United States, Tennessee

Research Site

Nashville, Tennessee, United States, 37203

Research Site

Nashville, Tennessee, United States, 37212

United States, Texas

Research Site

Houston, Texas, United States, 77030

United States, Virginia

Research Site

Fairfax, Virginia, United States, 22031

Austria

Research Site

Innsbruck, Austria, 6020

Research Site

Salzburg, Austria, 5020

Research Site

Wien, Austria, 1140

Research Site

Wien, Austria, 1210

Canada, Alberta

Research Site

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

Research Site

Brampton, Ontario, Canada, L6R 3J7

Research Site

Ottawa, Ontario, Canada, K1H 8L6

Research Site

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Research Site

Montreal, Quebec, Canada, H2X 3E4

France

Research Site

Bordeaux, France, 33076

Research Site

Nantes Cedex 1, France, 44093

Research Site

Paris, France, 75877

Research Site

Villejuif, France, 94800

Germany

Research Site

Berlin, Germany, 12203

Research Site

Esslingen a.N., Germany, 73730

Research Site

Grosshansdorf, Germany, 22927

Research Site

Heidelberg, Germany, 69126

Research Site

Köln, Germany, 50924

Israel

Research Site

Haifa, Israel, 31096

Research Site

Kfar Saba, Israel, 95847

Research Site

Petah Tikva, Israel, 49100

Research Site

Ramat Gan, Israel, 5265601

Korea, Republic of

Research Site

Seoul, Korea, Republic of, 03080

Research Site

Seoul, Korea, Republic of, 05505

Research Site

Seoul, Korea, Republic of, 6351

Spain

Research Site

Barcelona, Spain, 08036

Research Site

Madrid, Spain, 28007

Research Site

Madrid, Spain, 28034

Research Site

Sevilla, Spain, 41009

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: John Heymach, M.D, Ph.D; The University of Texas MD Anderson Cancer Center

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03334617
• Other Study ID Numbers: D6185C00001; 138050 ( Registry Identifier: IND ); 2023-509004-15-00 ( Other Identifier: EU CT number ); 2017-002208-28 ( EudraCT Number )
• First Posted: November 7, 2017
• Last Update Posted: March 15, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by AstraZeneca:

Non-small cell lung cancer; NSCLC; anti-PD-1/PD-L1; umbrella study; Durvalumab; MEDI4736; Olaparib; AZD2281; AZD9150; AZD6738; Vistusertib; AZD2014; Oleclumab; MEDI9447; Trastuzumab deruxtecan; DS-8201a; cediranib; AZD2171

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Trastuzumab; Durvalumab; Olaparib; Cediranib; Trastuzumab deruxtecan; Antineoplastic Agents, Immunological; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs