NCT02250326: abound2L+

Safety and Efficacy Study of Nab®-Paclitaxel With CC-486 or Nab®-Paclitaxel With Durvalumab, and Nab®-Paclitaxel Monotherapy as Second/Third-line Treatment for Advanced Non-small Cell Lung Cancer

Completed Phase 2 Results posted Last updated 19 September 2024

What this trial tests

Phase 2 trial testing nab-paclitaxel IV in Carcinoma, Non-Small-Cell Lung in 240 participants. Completed in 17 August 2023.

Timeline

7 January 2015

Primary endpoint
17 July 2017

17 August 2023

Quick facts

Lead sponsor	Celgene
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	240
Start date	7 January 2015
Primary completion	17 July 2017
Estimated completion	17 August 2023
Sites	34 locations across France, Italy, United Kingdom, Germany, Canada, United States, Spain

Drugs / interventions tested

• nab-paclitaxel IV — full drug profile →
• CC-486
• Duravalumab — full drug profile →

Conditions studied

• Carcinoma, Non-Small-Cell Lung — all drugs for Carcinoma, Non-Small-Cell Lung →

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. 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.

Kaplan Meier Estimate of Progression-Free Survival (PFS) as Assessed by the Investigator Primary · From date of first dose of IP to DP; up to data cut-off date of 30 August (Aug) 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 December (Dec) 2017 for Durva + nab-paclitaxel; participants were followed for PFS for up to 18 months

Progression-free survival was defined as the time in months from the date of randomization/assignment to the date of disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria documented by computed tomography (CT) scan, not including symptomatic deterioration, or death (any cause) on or prior to the clinical cut-off date, which ever occurred earlier. Participants who did not have disease progression and had not died, regardless of whether they were discontinued from treatment, were censored at the date of last tumor assessment, on or prior to t

Group	Value	95% CI
Nab-Paclitaxel + CC-486	3.2	2.30 – 4.30
Nab-Paclitaxel + Durvalumab	4.5	3.45 – 5.88
Nab-Paclitaxel Alone	4.2	2.79 – 5.06

Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) According to RECIST V 1.1 Criteria Secondary · Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

Disease control rate was defined as the percentage of participants who had a CR, PR or SD during the course of the study, according to RECIST version 1.1 criteria, as evaluated by the investigator. RECIST Version 1.1 criteria is defined as follows: - Complete Response is the disappearance of all target lesions; - Partial Response is at least a 30% decrease in the sum of diameters of target lesions from baseline; - Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease. Responses were evaluated every 6 weeks.

Group	Value	95% CI
Nab-Paclitaxel + CC-486	65.4	54.0 – 75.7
Nab-Paclitaxel + Durvalumab	70.9	59.6 – 80.6
Nab-Paclitaxel Alone	67.5	56.1 – 77.6

Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST V 1.1 Criteria Secondary · Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

Overall Response was defined as percentage of participants who achieved a radiologic confirmed complete response or partial response according to RECIST V 1.1 criteria and compared with baseline among all tumor assessments, where baseline was the last CT obtained prior to or on Day 1 of treatment. Per RECIST V 1.1 criteria, a CR is defined as a disappearance of all target lesions; a PR is defined as having at least a 30% decrease in the sum of diameters of target lesions from baseline. Responses were evaluated every 6 weeks.

Group	Value	95% CI
Nab-Paclitaxel + CC-486	13.6	7.0 – 23.0
Nab-Paclitaxel + Durvalumab	27.8	18.3 – 39.1
Nab-Paclitaxel Alone	16.3	8.9 – 26.2

Kaplan Meier Estimate of Overall Survival (OS) Secondary · Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; participants were followed for overall survival up to 30 months

Overall survival was defined as the time in months between randomization/treatment assignment and death from any cause. Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off, whichever was earlier. Participants who were lost to follow-up prior to the end of the study or who were withdrawn from the study were censored at the time of last contact.

Group	Value	95% CI
Nab-Paclitaxel + CC-486	8.1	6.64 – 11.86
Nab-Paclitaxel + Durvalumab	10.1	7.75 – NA
Nab-Paclitaxel Alone	17.0	8.21 – NA

Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Entire Treatment Period Secondary · TEAEs were collected up to 4 weeks after receiving last dose of investigational product (IP) for nab-paclitaxel and CC-486 + nab-paclitaxel, and up to 90 days after the last IP dose for Durva + nab-paclitaxel; TEAEs were collected up to 354 weeks

TEAEs were defined as any adverse event or serious adverse event that occurred or worsened on or after the day of the first dose of the IP through 28 days after the last dose of IP for Arms A and C or up to 90 days after the last dose for Arm B, and those SAEs made known to the investigator at any time thereafter that are suspected of being related to IP. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth

TEAE

Group	Value	95% CI
Nab-Paclitaxel + CC-486	79
Nab-Paclitaxel + Durvalumab	78
Nab-Paclitaxel	78

Serious TEAE

Group	Value	95% CI
Nab-Paclitaxel + CC-486	30
Nab-Paclitaxel + Durvalumab	44
Nab-Paclitaxel	30

Grade (GR) 3/4 TEAE

Group	Value	95% CI
Nab-Paclitaxel + CC-486	48
Nab-Paclitaxel + Durvalumab	57
Nab-Paclitaxel	47

Grade 3 or Higher

Group	Value	95% CI
Nab-Paclitaxel + CC-486	49
Nab-Paclitaxel + Durvalumab	59
Nab-Paclitaxel	47

Treatment Related TEAE

Group	Value	95% CI
Nab-Paclitaxel + CC-486	74
Nab-Paclitaxel + Durvalumab	72
Nab-Paclitaxel	68

Treatment Related Serious TEAE

Group	Value	95% CI
Nab-Paclitaxel + CC-486	11
Nab-Paclitaxel + Durvalumab	20
Nab-Paclitaxel	5

Treatment Related GR 3 or Higher TEAE

Group	Value	95% CI
Nab-Paclitaxel + CC-486	32
Nab-Paclitaxel + Durvalumab	36
Nab-Paclitaxel	25

TEAE With Action to Reduce/Interrupt IP

Group	Value	95% CI
Nab-Paclitaxel + CC-486	49
Nab-Paclitaxel + Durvalumab	59
Nab-Paclitaxel	38

Percentage of Participants Who Discontinued Study Treatment Secondary · Up to 30 Aug 2017 for CC-486 + nab-paclitaxel and 26 Nov 2019 for nab-paclitaxe and 20 Jul 2023 for Durva + nab-paclitaxel (up to 445 weeks)

The discontinuation rate was defined as the percentage of participants who had study drug discontinued and was assessed throughout the conduct of the study.

Group	Value	95% CI
Nab-Paclitaxel + CC-486	100.0
Nab-Paclitaxel + Durvalumab	100.0
Nab-Paclitaxel	100.0

Dose Intensity Per Week of Nab-Paclitaxel Secondary · Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

Dose intensity was the cumulative dose divided by the dosing period in weeks.

Group	Value	95% CI
Nab-Paclitaxel + CC-486	54.73	± 11.390
Nab-Paclitaxel + Durvalumab	57.18	± 13.605
Nab-Paclitaxel Alone	58.61	± 14.893

Dose Intensity Per Week of CC-486 Secondary · Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

Dose intensity was the cumulative dose divided by the dosing period in weeks.

Group	Value	95% CI
Nab-Paclitaxel + CC-486	716.66	± 220.945

Dose Intensity Per Week of Durvalumab Secondary · Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

Dose intensity was the cumulative dose divided by the dosing period in weeks.

Group	Value	95% CI
Nab-Paclitaxel + Durvalumab	279.96	± 97.304

Percentage of Participants With Study Drug Dose Reductions Secondary · Up to 16 Jan 2017 for CC-486 + nab-paclitaxel and up to 26 Nov 2019 for nab-paclitaxel and Durva + nab-paclitaxel (up to 255 weeks)

A dose reduction occurred when the dose assigned at a visit was lower than the dose assigned at the previous visit. Dose reductions were typically caused by clinically significant laboratory abnormalities and/or treatment emergent adverse events or toxicities.

Nab-Paclitaxel

Group	Value	95% CI
Nab-Paclitaxel + CC-486	10.1
Nab-Paclitaxel + Durvalumab	14.1
Nab-Paclitaxel Alone	10.1

CC-486

Group	Value	95% CI
Nab-Paclitaxel + CC-486	20.3

Durvalumab (Reductions Not Allowed per Protocol)

Group	Value	95% CI
Nab-Paclitaxel + Durvalumab	0.0

Adverse events — posted to ClinicalTrials.gov

Time frame: SAEs and AEs were collected up to 4 weeks after receiving last dose of investigational product (IP) for nab-paclitaxel and CC-486 + nab-paclitaxel, and up to 90 days after the last IP dose for Durva + nab-paclitaxel; (Up to 354 weeks). Participants were assessed for all-cause mortality from their first dose to study completion (Up to 449 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nab-Paclitaxel + CC-486

Serious: 30/79 (38%)

Deaths: 62/81

Nab-Paclitaxel + Durvalumab

Serious: 44/78 (56%)

Deaths: 48/79

Nab-Paclitaxel

Serious: 30/79 (38%)

Deaths: 50/80

Serious adverse events (91 terms)

Reaction	System	Nab-Paclitaxel + CC-486	Nab-Paclitaxel + Durvalumab	Nab-Paclitaxel
Pneumonia	Infections and infestations	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—
Adrenal insufficiency	Endocrine disorders	—	—	—
Pyrexia	General disorders	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
General physical health deterioration	General disorders	—	—	—
Performance status decreased	General disorders	—	—	—
Lung infection	Infections and infestations	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Epilepsy	Nervous system disorders	—	—	—
Seizure	Nervous system disorders	—	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—	—
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—

Other adverse events (72 terms — click to expand)

Reaction	System	Nab-Paclitaxel + CC-486	Nab-Paclitaxel + Durvalumab	Nab-Paclitaxel
Nausea	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—
Fatigue	General disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Pyrexia	General disorders	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Respiratory tract infection	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Paraesthesia	Nervous system disorders	—	—	—
Weight decreased	Investigations	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Dizziness	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Non-cardiac chest pain	General disorders	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—

Most-reported serious reactions: Pneumonia, Dyspnoea, Pleural effusion, Adrenal insufficiency, Pyrexia, Lower respiratory tract infection, Pulmonary embolism, Respiratory failure.

Data from ClinicalTrials.gov NCT02250326 adverse events section.

Sponsor's own description

This is a Phase 2, open-label, multicenter study to assess the efficacy and safety of second/third-line treatment with nab-paclitaxel in combination with the epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab, and nab-paclitaxel monotherapy in subjects with advanced non-small cell lung cancer (NSCLC).

Publications & conference data

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

1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
   Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
2. Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets.
   Yang J, Xu J, Wang W, Zhang B, et al · · 2023 · cited 251× · PMID 37217462 · DOI 10.1038/s41392-023-01480-x
3. Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.
   Wang Z, Wu X. · · 2020 · cited 147× · PMID 32875727 · DOI 10.1002/cam4.3410
4. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.
   Nepali K, Liou JP. · · 2021 · cited 122× · PMID 33840388 · DOI 10.1186/s12929-021-00721-x
5. Epigenetics in non-small cell lung cancer: from basics to therapeutics.
   Ansari J, Shackelford RE, El-Osta H. · · 2016 · cited 117× · PMID 27186511 · DOI 10.21037/tlcr.2016.02.02
6. Advances in epigenetic therapeutics with focus on solid tumors.
   Jin N, George TL, Otterson GA, Verschraegen C, et al · · 2021 · cited 87× · PMID 33879235 · DOI 10.1186/s13148-021-01069-7
7. Emerging therapeutic agents for lung cancer.
   Dholaria B, Hammond W, Shreders A, Lou Y. · · 2016 · cited 66× · PMID 27938382 · DOI 10.1186/s13045-016-0365-z
8. Novel chemotherapy regimens for advanced lung cancer: have we reached a plateau?
   Baxevanos P, Mountzios G. · · 2018 · cited 54× · PMID 29862228 · DOI 10.21037/atm.2018.04.04