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)

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).

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Olaparib; Drug: AZD9150; Drug: AZD6738; Drug: Vistusertib; Drug: Oleclumab; Drug: trastuzumab deruxtecan; Drug: cediranib; Drug: AZD6738 (ceralasertib); Drug: AZD6738 (ceralasertib); Drug: AZD6738 (ceralasertib) (240 mg or 160 mg); Drug: AZD6738 (ceralasertib) 7 days monotherapy

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 Type: Interventional
• Enrollment (Actual): 531
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Research Site
  • Salzburg, Austria, 5020
    • Research Site
  • Wien, Austria, 1140
    • Research Site
  • Wien, Austria, 1210
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Research Site
• France
  • Bordeaux, France, 33076
    • Research Site
  • Nantes Cedex 1, France, 44093
    • Research Site
  • Paris, France, 75877
    • Research Site
  • Villejuif, France, 94800
    • Research Site
• Germany
  • 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
    • Research Site
• Israel
  • Haifa, Israel, 31096
    • Research Site
  • Kfar Saba, Israel, 95847
    • Research Site
  • Petah Tikva, Israel, 49100
    • Research Site
  • Ramat Gan, Israel, 5265601
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 6351
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
• United States
  • California
    • 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
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Research Site
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • New York, New York, United States, 10032
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15232
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
    • Nashville, Tennessee, United States, 37212
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / 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.; 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); durvalumab given in combination with AZD6738 (D15-D28)	Drug: Durvalumab; Durvalumab given IV at 1500 mg Q4W ±2 days; 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.; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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
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.
Overall surival (OS)	Assessment of the anti-tumour activity of each therapy.	Through to study completion, up to 4.5 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Estimated): September 4, 2024
• Study Completion (Estimated): September 4, 2024

Study Registration Dates

• First Submitted: September 22, 2017
• First Submitted That Met QC Criteria: November 3, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Non-small cell lung cancer; Olaparib; Durvalumab; MEDI4736; DS-8201a; anti-PD-1/PD-L1; umbrella study; AZD2281; AZD9150; AZD6738; Vistusertib; AZD2014; Oleclumab; MEDI9447; Trastuzumab deruxtecan; cediranib; AZD2171
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Poly(ADP-ribose) Polymerase Inhibitors; Immunoconjugates; Trastuzumab; Olaparib; Durvalumab; Cediranib; Trastuzumab deruxtecan
• Other Study ID Numbers: D6185C00001; 2017-002208-28 (EudraCT Number); 138050 (Registry Identifier: IND); 2023-509004-15-00 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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