Durvalumab and Tremelimumab for Adjuvant Therapy of Resected NSCLC

NCT03130764 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: AAAQ8535
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Despite aggressive surgery and chemotherapy, the risk of lung cancer recurrence remains high in most patients. This study aims to determine if a novel immune therapy consisting of two drugs is feasible and potentially increases the chance of cure in lung cancer patients after surgery and standard chemotherapy. The immune-based therapy being given in this study consists of two medications named durvalumab and tremelimumab.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• The percentage rate of induced T-cell response in resected NSCLC patients

  An induced T-cell response is defined as T-cell activity against a tumor neoantigen detected in T-cells isolated from PBMCs collected at any timepoint after initiation of durvalumab-tremelimumab.

  Upto 1 year

Secondary Outcomes (2)

• Percentage of patients that complete at least 80% of the prescribed study treatments.

  Upto 2 years

• Disease Free Survival Rate (DFS)

  Upto 12 Months

Study Arms (1)

Durvalumab/Tremelimumab

EXPERIMENTAL

Patients with resected stage IB-IIIA NSCLC who have completed standard adjuvant therapy (as recommended by the treating physician) to receive durvalumab-tremelimumab will be enrolled. Patients will receive durvalumab (20 mg/kg) intravenously every 4 weeks for 1 year and tremelimumab (1 mg/kg) intravenously every 4 weeks for 4 doses.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

1500 mg, IV over 1 hour Every 4 weeks for 1 year

Also known as: MEDI4736

Durvalumab/Tremelimumab

Tremelimumab DRUG

75 mg, IV over 1 hour Every 4 weeks for 4 doses

Also known as: CP-675,206

Durvalumab/Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Adequate tissue must have been obtained from surgical intervention to satisfy biospecimen requirements of study (collected under biospecimen collection protocols; either AAAO5706 or AAAR1327).
• Histologically or cytologically confirmed squamous or non-squamous NSCLC.
• Stage IB-IIIA
• R0 or R1 resection
• Patients must have completed surgical resection and adjuvant chemotherapy (adjuvant radiotherapy excluded) with no significant persisting treatment related toxicity (grade 1 toxicity per CTCAE v4.0 allowed) as determined by the treating physician.
• Study treatment must begin within 30 days of surgical resection or adjuvant treatment. This timeline may be extended if further time for recovery from treatment related toxicities is required.
• Age ≥18 years; as no dosing or adverse event data are currently available on the use of durvalumab-tremelimumab in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status ≤1 (Karnofsky ≥70%).
• Patients must have normal organ and marrow function as defined below:
• Hemoglobin \>or = 9.0 g/dL
• Absolute neutrophil count ≥1.5 x 109/L
• Platelets ≥100 x 109/L
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

You may not qualify if:

• Pre- or post-operative radiotherapy.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Participation in another clinical study with an investigational product during the last 4 weeks
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Any unresolved toxicity ( \> CTCAE grade 2) from previous anti-cancer therapy.
• Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• Active hepatitis B or C (defined as positive Hepatitis B surface antigen, hepatitis C antibody)
• History of HIV infection
• History of interstitial lung disease/pneumonitis from any cause
• Never-smokers if EGFR/ALK testing results are unknown
• Patients with NSCLC that harbors an ALK rearrangement, or sensitizing EGFR mutation.

Sponsors & Collaborators

• Columbia University: lead

Related Publications (6)

• Antonia S, Goldberg SB, Balmanoukian A, Chaft JE, Sanborn RE, Gupta A, Narwal R, Steele K, Gu Y, Karakunnel JJ, Rizvi NA. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016 Mar;17(3):299-308. doi: 10.1016/S1470-2045(15)00544-6. Epub 2016 Feb 6.

  PMID: 26858122 BACKGROUND

• Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.

  PMID: 21351269 BACKGROUND

• Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, Postmus PE, Rusch V, Sobin L; International Association for the Study of Lung Cancer International Staging Committee; Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007 Aug;2(8):706-14. doi: 10.1097/JTO.0b013e31812f3c1a.

  PMID: 17762336 BACKGROUND

• Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.

  PMID: 26412456 BACKGROUND

• Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-1550. doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19.

  PMID: 26712084 BACKGROUND

• Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbe C, Ferraresi V, Smylie M, Weber JS, Maio M, Konto C, Hoos A, de Pril V, Gurunath RK, de Schaetzen G, Suciu S, Testori A. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 May;16(5):522-30. doi: 10.1016/S1470-2045(15)70122-1. Epub 2015 Mar 31.

  PMID: 25840693 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Adrian Sacher, M.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 26, 2017
• Study Start: March 1, 2017
• Primary Completion: November 30, 2017
• Study Completion: November 30, 2017
• Last Updated: December 6, 2017

Record last verified: 2017-12