NCT02879617

A Clinical Trial of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer Patients

Completed Phase 2 Results posted Last updated 5 January 2024

What this trial tests

Phase 2 trial testing durvalumab in Non-Small Cell Lung Cancer NSCLC in 47 participants. Completed in 4 June 2022.

Timeline

4 April 2017

Primary endpoint
4 June 2022

4 June 2022

Quick facts

Lead sponsor	Academic Thoracic Oncology Medical Investigators Consortium
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	47
Start date	4 April 2017
Primary completion	4 June 2022
Estimated completion	4 June 2022
Sites	2 locations across United States

Drugs / interventions tested

• durvalumab — full drug profile →

Conditions studied

• Non-Small Cell Lung Cancer NSCLC — all drugs for Non-Small Cell Lung Cancer NSCLC →

Sponsor

Academic Thoracic Oncology Medical Investigators Consortium

Who can join

18 and older, any sex, with Non-Small Cell Lung Cancer NSCLC. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) Primary · Up to 30 months

Median length of time from the start of treatment from start of treatment to death from any cause.

Group	Value	95% CI
Durvalumab	6.00	4.00 – 10.00

Overall Survival (OS12) Primary · At 12 months

Number of patients alive at 12 months post start of treatment.

Group	Value	95% CI
Durvalumab	15

Overall Survival (OS24) Primary · At 24 months

Number of patients alive at 24 months post start of treatment.

Group	Value	95% CI
Durvalumab	8

Treatment-related Adverse Events ≥ Grade 3 Primary · Up to 30 months

Number of participants with ≥ Grade 3 adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 that are at least possibly related to study treatment.

Group	Value	95% CI
Durvalumab	1
Durvalumab	1
Durvalumab	1
Durvalumab	1

Progression-Free Survival (PFS) Secondary · Up to 30 months

Median duration of time from start of treatment to time of progression or death, whichever occurs first. Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:Appearance of one or more new

Group	Value	95% CI
Durvalumab	3.00	1.00 – 4.00

Progression-Free Survival (PFS) at 12 Months Secondary · At 12 months

Number of patients without progressive disease or death at 12 months from start of treatment. Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Appearance of one or more new lesions an

Group	Value	95% CI
Durvalumab	7

Progression-Free Survival (PFS) at 24 Months Secondary · At 24 months

Number of patients without progressive disease or death at 24 months from start of treatment Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:Appearance of one or more new lesions and/

Group	Value	95% CI
Durvalumab	4

Progression-Free Survival (PFS) by PD-L1 Expression at 12 Months Secondary · At 12 months

Number of patients of know PD-L1 status without progressive disease or death at 12 months from start of treatment. Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Appearance of one o

PD-L1=0

Group	Value	95% CI
Durvalumab	1

0%<PD-L1<50%

Group	Value	95% CI
Durvalumab	4

PD-L1≥50%

Group	Value	95% CI
Durvalumab	2

Progression-Free Survival (PFS) by PD-L1 Expression Status at 24 Months Secondary · At 24 months

Number of patients of know PD-L1 status without progressive disease or death at 24 months from start of treatment Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:Appearance of one or

PD-L1=0

Group	Value	95% CI
Durvalumab	0

0%<PD-L1<50%

Group	Value	95% CI
Durvalumab	3

PD-L1≥50%

Group	Value	95% CI
Durvalumab	1

Overall Survival by PD-L1 Expression Status at 12 Months Secondary · At 12 months

Number of patients with know PD-L1 status that are alive at 12 months post start of treatment.

PD-L1=0

Group	Value	95% CI
Durvalumab	5

0%<PD-L1<50%

Group	Value	95% CI
Durvalumab	5

PD-L1≥50%

Group	Value	95% CI
Durvalumab	3

Overall Survival by PD-L1 Expression Status at 24 Months Secondary · At 24 months

Number of patients with know PD-L1 status that are alive at 24 months post start of treatment.

PD-L1=0

Group	Value	95% CI
Durvalumab	3

0%<PD-L1<50%

Group	Value	95% CI
Durvalumab	3

PD-L1≥50%

Group	Value	95% CI
Durvalumab	2

Overall Response Rate (ORR) Secondary · Up to 30 months

Percentage of patients with a Best Response of Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). Per RECIST v1.0, for target lesions: PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither PR nor PD (target lesions); persistence of 1 or more non-target lesions and/or the maintenance of tumor marker levels above normal limits. PD: at least a 20% increase in sum of diameters (target lesions), taking as reference the smallest sum on study (includes baseline sum if smallest on study). In addition

Partial Response (PD)

Group	Value	95% CI
Durvalumab	26

Stable Disease (SD)

Group	Value	95% CI
Durvalumab	47

Progressive Disease (PD)

Group	Value	95% CI
Durvalumab	26

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events data were collected for up to 33 months per patient, and up to. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Durvalumab

Serious: 26/47 (55%)

Deaths: 40/47

Serious adverse events (45 terms)

Reaction	System	Durvalumab
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Lung infection	Infections and infestations	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—
Atrial fibrillation	Cardiac disorders	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—
Anemia	Blood and lymphatic system disorders	—
Cardiac arrest	Cardiac disorders	—
Non-cardiac chest pain	General disorders	—
Urinary tract infection	Infections and infestations	—
Fall	Injury, poisoning and procedural complications	—
Dehydration	Metabolism and nutrition disorders	—
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Aspiration	Respiratory, thoracic and mediastinal disorders	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—
Respiratory, thoracic and mediastinal disorders - Other, specify	Respiratory, thoracic and mediastinal disorders	—
Pericardial effusion	Cardiac disorders	—
Colitis	Gastrointestinal disorders	—
Lower gastrointestinal hemorrhage	Gastrointestinal disorders	—
Death NOS	General disorders	—
Fatigue	General disorders	—
Pain	General disorders	—
Sepsis	Infections and infestations	—
Fracture	Injury, poisoning and procedural complications	—
Injury, poisoning and procedural complications - Other, specify	Injury, poisoning and procedural complications	—

Other adverse events (261 terms — click to expand)

Reaction	System	Durvalumab
Anemia	Blood and lymphatic system disorders	—
Hypoalbuminemia	Metabolism and nutrition disorders	—
Lymphocyte count decreased	Investigations	—
Fatigue	General disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Hyponatremia	Metabolism and nutrition disorders	—
Proteinuria	Renal and urinary disorders	—
Hypertension	Vascular disorders	—
Alkaline phosphatase increased	Investigations	—
Sinus tachycardia	Cardiac disorders	—
Anorexia	Metabolism and nutrition disorders	—
Pain	General disorders	—
Creatinine increased	Investigations	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—
Alanine aminotransferase increased	Investigations	—
Investigations - Other, specify	Investigations	—
Weight loss	Investigations	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—
Edema limbs	General disorders	—
Urinary tract infection	Infections and infestations	—
Hyperuricemia	Metabolism and nutrition disorders	—
Hypocalcemia	Metabolism and nutrition disorders	—
Hypokalemia	Metabolism and nutrition disorders	—
Anxiety	Psychiatric disorders	—
Hematuria	Renal and urinary disorders	—
Wheezing	Respiratory, thoracic and mediastinal disorders	—
Nausea	Gastrointestinal disorders	—
INR increased	Investigations	—
Hypercalcemia	Metabolism and nutrition disorders	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—
Sinus bradycardia	Cardiac disorders	—
Diarrhea	Gastrointestinal disorders	—
Lung infection	Infections and infestations	—
GGT increased	Investigations	—
Dehydration	Metabolism and nutrition disorders	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Laryngeal hemorrhage	Respiratory, thoracic and mediastinal disorders	—
Constipation	Gastrointestinal disorders	—
Non-cardiac chest pain	General disorders	—

Most-reported serious reactions: Dyspnea, Lung infection, Hypoxia, Pleural effusion, Atrial fibrillation, Respiratory failure, Anemia, Cardiac arrest.

Data from ClinicalTrials.gov NCT02879617 adverse events section.

Sponsor's own description

This is a single-arm phase II clinical trial evaluating the safety and efficacy of the PD-L1 inhibitor durvalumab as first-line therapy in 47 patients with advanced NSCLC and ECOG Performance Status 2 (PS2).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort.
   Prelaj A, Ferrara R, Rebuzzi SE, Proto C, et al · · 2019 · cited 64× · PMID 31817541 · DOI 10.3390/cancers11121954
2. Successes and failures: what did we learn from recent first-line treatment immunotherapy trials in non-small cell lung cancer?
   Remon J, Besse B, Soria JC. · · 2017 · cited 60× · PMID 28285592 · DOI 10.1186/s12916-017-0819-3
3. Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab.
   Dumenil C, Massiani MA, Dumoulin J, Giraud V, et al · · 2018 · cited 45× · PMID 29684049 · DOI 10.1371/journal.pone.0195945
4. Performance Status and Age as Predictors of Immunotherapy Outcomes in Advanced Non-Small-Cell Lung Cancer.
   Ahmed T, Lycan T, Dothard A, Ehrlichman P, et al · · 2020 · cited 36× · PMID 32089478 · DOI 10.1016/j.cllc.2020.01.001
5. Safety and efficacy of durvalumab (MEDI4736) in various solid tumors.
   Yang H, Shen K, Zhu C, Li Q, et al · · 2018 · cited 31× · PMID 30013326 · DOI 10.2147/dddt.s162214
6. First-line immunotherapy in non-small cell lung cancer patients with poor performance status: a systematic review and meta-analysis.
   Facchinetti F, Di Maio M, Perrone F, Tiseo M. · · 2021 · cited 30× · PMID 34295688 · DOI 10.21037/tlcr-21-15
7. First-line immunotherapy in advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an International Expert Panel Meeting by the Italian Association of Thoracic Oncology.
   Gridelli C, Peters S, Mok T, Forde PM, et al · · 2022 · cited 29× · PMID 34922299 · DOI 10.1016/j.esmoop.2021.100355
8. SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2.
   Mark M, Froesch P, Eboulet EI, Addeo A, et al · · 2021 · cited 15× · PMID 33130956 · DOI 10.1007/s00262-020-02757-8