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

NCT03334617 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 4 other identifiers: D6185C000011380502023-509004-15-002017-002208-28
• Study Type: interventional
• Target: 528
• Locations: 8 countries
• Sites: 45

Brief Summary

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

Conditions

Non-Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)

  Objective response was defined as participants with a confirmed investigator-assessed response complete response (CR) or partial response (PR) based on RECIST v 1.1. The CR is defined as disappearance of all target (TL) and non-target lesions (NTL), and any pathological lymph node (whether target or nontarget) must have reduction in short axis to \<10 mm. The PR is defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum diameters, as long as criteria for progressive disease (PD) are not met. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from date of first documentation. Percentage of participants with objective response was reported.

  Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)

Secondary Outcomes (10)

• Overall Survival (OS)

  Every 3 months after safety follow-up visit (90 days after study drug discontinuation) until planned database lock for a module (either 12 months after last participant has started treatment or when 75% of participants died) (approximately up to 2 years)

• Progression-Free Survival (PFS) Per RECIST v1.1

  Every 3 months after safety follow-up visit (90 days after study drug discontinuation) until planned database lock for a module (either 12 months after last participant has started treatment or when 75% of participants died) (approximately up to 2 years)

• Best Percentage Change From Baseline in Tumour Size

  Baseline (<=28 days prior to starting treatment) then every 6 weeks for first 24 weeks relative to the date of first dose/combination therapy (Cycle 1 Day 1), then every 8 weeks (except Module 6)/9 weeks (Module 6) thereafter (approximately up to 2 years)

• Percentage of Participants With Disease Control (DC) Per RECIST v1.1

  At 12 and 24 weeks after the start of study drug

• Duration of Response (DoR) Per RECIST v1.1

  Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)

Study Arms (22)

Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg

EXPERIMENTAL

Participants with detectable aberrations, mutation detected in a homologous recombination repair gene (HRRm) will receive IV infusion of durvalumab 1500 mg every 4 weeks (Q4W) in combination with oral olaparib 300 mg (2 × 150 mg) tablets twice a day (BD) until disease progression is confirmed.

Drug: Durvalumab; Drug: Olaparib

Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg

EXPERIMENTAL

Participants with detectable aberrations in liver kinase B1 (LKB1) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed.

Drug: Durvalumab; Drug: Olaparib

Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg

EXPERIMENTAL

Participants who had anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (primary resistance; PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed.

Drug: Durvalumab; Drug: Olaparib

Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg

EXPERIMENTAL

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (acquired resistance; ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed.

Drug: Durvalumab; Drug: Olaparib

Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg

EXPERIMENTAL

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Danvatirsen

Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg

EXPERIMENTAL

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Danvatirsen

Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg

EXPERIMENTAL

Participants who are ataxia telangiectasia mutated (ATM)-deficiecy will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD in each cycle between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Ceralasertib

Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg

EXPERIMENTAL

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Ceralasertib

Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg

EXPERIMENTAL

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Ceralasertib

Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg

EXPERIMENTAL

Participants with detectable genetic amplifications in rapamycin-insensitive companion of mechanistic target of rapamycin complex-2 (RICTOR) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral vistusertib 125 mg tablets BD on an intermittent dosing schedule of 2 days on, 5 days off, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Vistusertib

Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg

EXPERIMENTAL

Participants with high expression of cluster of differentiation 73 (CD73) will receive IV infusion of oleclumab 3000 mg every 2 weeks (Q2W) for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Oleclumab

Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg

EXPERIMENTAL

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Oleclumab

Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg

EXPERIMENTAL

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Oleclumab

Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg

EXPERIMENTAL

Participants whose tumours express human epidermal growth factor receptor 2 (HER2) mutations will receive IV infusion of trastuzumab deruxtecan (T-DXd) 5.4 mg/kg every 3 weeks (Q3W) in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Trastuzumab deruxtecan

Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg

EXPERIMENTAL

Participants whose tumours harbour selected HER2 mutations will receive IV infusion of T-DXd 5.4 mg/kg Q3W in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Trastuzumab deruxtecan

Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg

EXPERIMENTAL

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral cediranib (AZD2171) 20 mg tablets daily for 5 days on, 2 days off (starting on Cycle 1 Day 1 of durvalumab), until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Cediranib

Module 8 Cohort A.8.ATM: Ceralasertib 240 mg

EXPERIMENTAL

Participants who are ATM-deficient or with detectable aberrations in the ATM gene will receive oral ceralasertib (AZD6738) 240 mg tablets BD from Day 1 to Day 14 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Ceralasertib

Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg

EXPERIMENTAL

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Ceralasertib

Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg

EXPERIMENTAL

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W plus oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Ceralasertib

Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg

EXPERIMENTAL

Participants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 160 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 160 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Ceralasertib

Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg

EXPERIMENTAL

Participants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Drug: Durvalumab; Drug: Ceralasertib

Module 11 Cohort C.11.240: AZD6738 240 mg

EXPERIMENTAL

Participants, independent of their molecular aberration status, will receive oral AZD6738 tablet 240 mg for 7 days (Days 1 to 7) in each 28-day cycle until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Drug: Ceralasertib

Interventions

Durvalumab DRUG

Participants will receive IV infusion of durvalumab as stated in arm description.

Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg; Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg; Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg; Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg; Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg; Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg; Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg; Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg; Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg; Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg; Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg; Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg; Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg; Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg; Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg; Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg; Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg; Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg; Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg; Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg

Danvatirsen DRUG

Participants will receive IV infusion of danvatirsen as stated in arm description.

Also known as: AZD9150

Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg; Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg

Ceralasertib DRUG

Participants will receive oral tablet of ceralasertib as stated in arm description.

Also known as: AZD6738

Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg; Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg; Module 11 Cohort C.11.240: AZD6738 240 mg; Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg; Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg; Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg; Module 8 Cohort A.8.ATM: Ceralasertib 240 mg; Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg; Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg

Vistusertib DRUG

Participants will receive oral tablets of vistusertib as stated in arm description.

Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg

Olaparib DRUG

Participants will receive oral tablets of olaparib as stated in arm description.

Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg; Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg; Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg; Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg

Oleclumab DRUG

Participants will receive IV infusion of oleclumab as stated in arm description.

Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg; Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg; Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg

Trastuzumab deruxtecan DRUG

Participants will receive IV infusion of trastuzumab deruxtecan as stated in arm description.

Also known as: T-DXd

Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg; Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg

Cediranib DRUG

Participants will receive oral tablets of cediranib as stated in arm description.

Also known as: AZD2171

Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age at the time of signing the informed consent form.
• Participant must have histologically or cytologically confirmed metastatic or locally advanced and recurrent non-small-cell lung cancer (NSCLC) which is progressing.
• Participants eligible for second- or later-line therapy, who must have received an anti-programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (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 participant must have had disease progression on a prior line of anti-PD-1/PD-L1 therapy.
• Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) performance status of 0 to 1, and a minimum life expectancy of 12 weeks.
• Participant 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 participants.

You may not qualify if:

• Participants whose tumour samples have targetable alterations in epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) at initial diagnosis are excluded. In addition, participants 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 hepatitis B virus \[HBV\] surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus (positive human immunodeficiency virus \[HIV\] 1/2 antibodies).
• Female participant who are pregnant or breastfeeding, or male or female participants 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.
• Participant has spinal cord compression or symptomatic brain metastases.
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Participants 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (45)

Research Site

Duarte, California, 91010, United States

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Fullerton, California, 92835, United States

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La Jolla, California, 92093, United States

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Los Angeles, California, 90095, United States

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Washington D.C., District of Columbia, 20016, United States

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Chicago, Illinois, 60637, United States

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Baltimore, Maryland, 21224, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02215, United States

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St Louis, Missouri, 63110, United States

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New York, New York, 10032, United States

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Philadelphia, Pennsylvania, 19111, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Nashville, Tennessee, 37203, United States

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Nashville, Tennessee, 37212, United States

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Houston, Texas, 77030, United States

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Fairfax, Virginia, 22031, United States

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Innsbruck, 6020, Austria

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Salzburg, 5020, Austria

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Vienna, 1140, Austria

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Vienna, 1210, Austria

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Edmonton, Alberta, T6G 1Z2, Canada

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Brampton, Ontario, L6R 3J7, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H2X 3E4, Canada

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Bordeaux, 33076, France

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Nantes, 44093, France

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Paris, 75877, France

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Villejuif, 94800, France

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Berlin, 12203, Germany

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Esslingen a.N., 73730, Germany

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Großhansdorf, 22927, Germany

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Heidelberg, 69126, Germany

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Haifa, 31096, Israel

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Kfar Saba, 95847, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 5265601, Israel

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Seoul, 03080, South Korea

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Seoul, 05505, South Korea

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Seoul, 6351, South Korea

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Barcelona, 08036, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Seville, 41009, Spain

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Related Publications (1)

• Besse B, Pons-Tostivint E, Park K, Hartl S, Forde PM, Hochmair MJ, Awad MM, Thomas M, Goss G, Wheatley-Price P, Shepherd FA, Florescu M, Cheema P, Chu QSC, Kim SW, Morgensztern D, Johnson ML, Cousin S, Kim DW, Moskovitz MT, Vicente D, Aronson B, Hobson R, Ambrose HJ, Khosla S, Reddy A, Russell DL, Keddar MR, Conway JP, Barrett JC, Dean E, Kumar R, Dressman M, Jewsbury PJ, Iyer S, Barry ST, Cosaert J, Heymach JV. Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. Nat Med. 2024 Mar;30(3):716-729. doi: 10.1038/s41591-024-02808-y. Epub 2024 Feb 13.

  PMID: 38351187 DERIVED

Related Links

• Redacted SAP
• Redacted CSP
• Redacted CSR synopsis

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; danvatirsen; ceralasertib; vistusertib; olaparib; trastuzumab deruxtecan; cediranib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Module 4 was prematurely discontinued by the sponsor for strategic reasons.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

+1-877-240-9479

Study Officials

• John Heymach, M.D, Ph.D

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, multi-centre, umbrella Phase II study in participants 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.

Study Record Dates

• First Submitted: September 22, 2017
• First Posted: November 7, 2017
• Study Start: December 18, 2017
• Primary Completion: September 13, 2024
• Study Completion (Estimated): September 11, 2026
• Last Updated: October 27, 2025
• Results First Posted: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

IL (4); DE (4); KR (3); US (17); CA (5); AU (4); ES (4); FR (4)