Study Summary
This trial will study the effects of the immunotherapy drug MEDI4736 in patients with stage III unresectable NSCLC who are also receiving concurrent chemoradiation therapy.
Eligible Conditions
- Non-Small Cell Lung Cancer
Treatment Effectiveness
Phase-Based Effectiveness
Phase 3
Study Objectives
2 Primary · 12 Secondary · Reporting Duration: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.
Year 4
Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL), Assessed Using European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30)
Malignant Neoplasms
Year 4
Time to Second Progression or Death (PFS2)
Year 4
Overall Survival
Percentage of Patients Alive at 24 Months (OS24)
Week 48
Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
Week 48
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab
Year 3
Proportion of Patients Alive and Progression Free at 12 Months From (APF12) Based on BICR Assessments According to RECIST 1.1
Proportion of Patients Alive and Progression Free at 18 Months From (APF18) Based on BICR Assessments According to RECIST 1.1
Year 4
Duration of Response (DoR) Based on BICR Assessments According to RECIST 1.1
Objective Response Rate (ORR) Based on BICR Assesments According to RECIST 1.1
Time to Death or Distant Metastasis (TTDM) Based on BICR Assessments According to RECIST 1.1
Year 3
Progression Free Survival Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Trial Safety
Phase-Based Safety
This is further along than 85% of similar trials
Side Effects for
Standard of Care (SoC)
23%Anaemia
23%Asthenia
20%Decreased appetite
17%Nausea
15%Rash
15%Fatigue
13%Neutropenia
13%Diarrhoea
12%Constipation
12%Alopecia
12%Pyrexia
11%Stomatitis
10%Neck pain
10%Neuropathy peripheral
8%Vomiting
8%Thrombocytopenia
8%Weight decreased
8%Dyspnoea
8%Cough
8%Hypomagnesaemia
8%Dysphagia
7%Dermatitis acneiform
7%Mucosal inflammation
7%Alanine aminotransferase increased
7%Headache
6%Aspartate aminotransferase increased
5%Gamma-glutamyltransferase increased
5%Leukopenia
4%Pruritus
4%Pneumonia
3%Blood alkaline phosphatase increased
3%Hypertension
3%Hyponatraemia
3%Insomnia
3%Hypercalcaemia
2%Sepsis
2%Hypothyroidism
1%Lung infection
1%Pneumonia aspiration
1%Respiratory failure
1%Death
1%Tumour haemorrhage
1%Device occlusion
1%Localised infection
1%Asphyxia
Awards & Highlights
All Individual Drugs Already Approved
Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.
Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.
Trial Design
2 Treatment Groups
MEDI4736
1 of 2
PLACEBO
1 of 2
Experimental Treatment
Non-Treatment Group
713 Total Participants · 2 Treatment Groups
Primary Treatment: MEDI4736 · Has Placebo Group · Phase 3
MEDI4736
Drug
Experimental Group · 1 Intervention: MEDI4736 · Intervention Types: DrugPLACEBO
Other
PlaceboComparator Group · 1 Intervention: PLACEBO · Intervention Types: OtherTreatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Durvalumab
FDA approved
Trial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. assessed until 13 feb 2017 dco; up to a maximum of approximately 3 years.
Who is running the clinical trial?
AstraZenecaLead Sponsor
4,051 Previous Clinical Trials
240,384,153 Total Patients Enrolled
Phil Dennis, MDStudy DirectorAstraZeneca
Eligibility Criteria
Age 18 - 130 · All Participants · 1 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:You are expected to live for at least another 12 weeks.
References
- Garassino, Marina C, Luis Paz-Ares, Rina Hui, Corinne Faivre-Finn, Alex Spira, David Planchard, Mustafa Özgüroğlu, et al.. 2021. “Patient-reported Outcomes with Durvalumab by PD-L1 Expression and Prior Chemoradiotherapy-related Variables in Unresectable Stage III Non-small-cell Lung Cancer”. Future Oncology. Future Medicine Ltd. doi:10.2217/fon-2020-1102.
- Mehra, Ranee, Candice Yong, Brian Seal, Marjolijn van Keep, Angie Raad, and Yiduo Zhang. 2021. “Cost-effectiveness of Durvalumab After Chemoradiotherapy in Unresectable Stage III NSCLC: A US Healthcare Perspective”. Journal of the National Comprehensive Cancer Network. Harborside Press, LLC. doi:10.6004/jnccn.2020.7621.
- Faivre-Finn, Corinne, David Vicente, Takayasu Kurata, David Planchard, Luis Paz-Ares, Johan F. Vansteenkiste, David R. Spigel, et al.. 2021. “Four-year Survival with Durvalumab After Chemoradiotherapy in Stage III Nsclc—an Update from the PACIFIC Trial”. Journal of Thoracic Oncology. Elsevier BV. doi:10.1016/j.jtho.2020.12.015.
- Faivre-Finn, Corinne, David R. Spigel, Suresh Senan, Corey Langer, Bradford A. Perez, Mustafa Özgüroğlu, Davey Daniel, et al.. 2021. “Impact of Prior Chemoradiotherapy-related Variables on Outcomes with Durvalumab in Unresectable Stage III NSCLC (PACIFIC)”. Lung Cancer. Elsevier BV. doi:10.1016/j.lungcan.2020.11.024.
- Paz-Ares, L., A. Spira, D. Raben, D. Planchard, B.C. Cho, M. Özgüroğlu, D. Daniel, et al.. 2020. “Outcomes with Durvalumab by Tumour PD-L1 Expression in Unresectable, Stage III Non-small-cell Lung Cancer in the PACIFIC Trial”. Annals of Oncology. Elsevier BV. doi:10.1016/j.annonc.2020.03.287.
- Gray, Jhanelle E., Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takayasu Kurata, et al.. 2020. “Three-year Overall Survival with Durvalumab After Chemoradiotherapy in Stage III Nsclc—update from PACIFIC”. Journal of Thoracic Oncology. Elsevier BV. doi:10.1016/j.jtho.2019.10.002.
- Hui, Rina, Mustafa Özgüroğlu, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Takashi Yokoi, et al.. 2019. “Patient-reported Outcomes with Durvalumab After Chemoradiotherapy in Stage III, Unresectable Non-small-cell Lung Cancer (PACIFIC): A Randomised, Controlled, Phase 3 Study”. The Lancet Oncology. Elsevier BV. doi:10.1016/s1470-2045(19)30519-4.
- Antonia, Scott J., Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takayasu Kurata, et al.. 2018. “Overall Survival with Durvalumab After Chemoradiotherapy in Stage III NSCLC”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1809697.
- Antonia, Scott J., Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takashi Yokoi, et al.. 2017. “Durvalumab After Chemoradiotherapy in Stage III Non–small-cell Lung Cancer”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1709937.
- Ouwens, Mario, Annie Darilay, Yiduo Zhang, Pralay Mukhopadhyay, Helen Mann, James Ryan, and Phillip A. Dennis. 2021. “Assessing the Influence of Subsequent Immunotherapy on Overall Survival in Patients with Unresectable Stage III Non–small Cell Lung Cancer from the PACIFIC Study”. Current Therapeutic Research. Elsevier BV. doi:10.1016/j.curtheres.2021.100640.
- Antonia, Scott J., Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, Takashi Yokoi, et al.. 2017. “Durvalumab After Chemoradiotherapy in Stage III Non–small-cell Lung Cancer”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejmoa1709937.
- Socinski, Mark A., Mustafa Özgüroğlu, Augusto Villegas, Davey Daniel, David Vicente, Shuji Murakami, Rina Hui, et al.. 2021. “Durvalumab After Concurrent Chemoradiotherapy in Elderly Patients with Unresectable Stage III Non–small–cell Lung Cancer (PACIFIC)”. Clinical Lung Cancer. Elsevier BV. doi:10.1016/j.cllc.2021.05.009.
- Naidoo, Jarushka, Johan F. Vansteenkiste, Corinne Faivre-Finn, Mustafa Özgüroğlu, Shuji Murakami, Rina Hui, Xavier Quantin, et al.. 2022. “Characterizing Immune-mediated Adverse Events with Durvalumab in Patients with Unresectable Stage III NSCLC: A Post-hoc Analysis of the PACIFIC Trial”. Lung Cancer. Elsevier BV. doi:10.1016/j.lungcan.2022.02.003.
- Spigel, David R., Corinne Faivre-Finn, Jhanelle E. Gray, David Vicente, David Planchard, Luis Paz-Ares, Johan F. Vansteenkiste, et al.. 2022. “Five-year Survival Outcomes from the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–small-cell Lung Cancer”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.21.01308.
- Senan, S., M. Özgüroğlu, D. Daniel, A. Villegas, D. Vicente, S. Murakami, R. Hui, et al.. 2022. “Outcomes with Durvalumab After Chemoradiotherapy in Stage IIIA-N2 Non-small-cell Lung Cancer: An Exploratory Analysis from the PACIFIC Trial”. ESMO Open. Elsevier BV. doi:10.1016/j.esmoop.2022.100410.
- Naidoo J, Vansteenkiste JF, Faivre-Finn C, Ozguroglu M, Murakami S, Hui R, Quantin X, Broadhurst H, Newton M, Thiyagarajah P, Antonia SJ. Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Lung Cancer. 2022 Apr;166:84-93. doi: 10.1016/j.lungcan.2022.02.003. Epub 2022 Feb 9.
- Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Ozguroglu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial. J Thorac Oncol. 2021 May;16(5):860-867. doi: 10.1016/j.jtho.2020.12.015. Epub 2021 Jan 19.
- Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Ozguroglu M; PACIFIC Investigators. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25.
- Socinski MA, Ozguroglu M, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Gray JE, Park K, Vincent M, Mann H, Newton M, Dennis PA, Antonia SJ. Durvalumab After Concurrent Chemoradiotherapy in Elderly Patients With Unresectable Stage III Non-Small-Cell Lung Cancer (PACIFIC). Clin Lung Cancer. 2021 Nov;22(6):549-561. doi: 10.1016/j.cllc.2021.05.009. Epub 2021 Jun 12.
- Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2. Erratum In: J Clin Oncol. 2022 Jun 10;40(17):1965.
- Garassino MC, Paz-Ares L, Hui R, Faivre-Finn C, Spira A, Planchard D, Ozguroglu M, Daniel D, Vicente D, Murakami S, Langer C, Senan S, Spigel D, Ryden A, Zhang Y, O'Brien C, Dennis PA, Antonia SJ. Patient-reported outcomes with durvalumab by PD-L1 expression and prior chemoradiotherapy-related variables in unresectable stage III non-small-cell lung cancer. Future Oncol. 2021 Apr;17(10):1165-1184. doi: 10.2217/fon-2020-1102. Epub 2021 Feb 15.
- Senan S, Ozguroglu M, Daniel D, Villegas A, Vicente D, Murakami S, Hui R, Faivre-Finn C, Paz-Ares L, Wu YL, Mann H, Dennis PA, Antonia SJ. Outcomes with durvalumab after chemoradiotherapy in stage IIIA-N2 non-small-cell lung cancer: an exploratory analysis from the PACIFIC trial. ESMO Open. 2022 Apr;7(2):100410. doi: 10.1016/j.esmoop.2022.100410. Epub 2022 Mar 2.
- Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, Cho BC, Planchard D, Paz-Ares L, Faivre-Finn C, Vansteenkiste JF, Spigel DR, Wadsworth C, Taboada M, Dennis PA, Ozguroglu M, Antonia SJ. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb;15(2):288-293. doi: 10.1016/j.jtho.2019.10.002. Epub 2019 Oct 14.
- Hui R, Ozguroglu M, Villegas A, Daniel D, Vicente D, Murakami S, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Gray JE, Ryden A, Viviers L, Poole L, Zhang Y, Dennis PA, Antonia SJ. Patient-reported outcomes with durvalumab after chemoradiotherapy in stage III, unresectable non-small-cell lung cancer (PACIFIC): a randomised, controlled, phase 3 study. Lancet Oncol. 2019 Dec;20(12):1670-1680. doi: 10.1016/S1470-2045(19)30519-4. Epub 2019 Oct 7.
- Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Ozguroglu M; PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. doi: 10.1056/NEJMoa1709937. Epub 2017 Sep 8.
- Faivre-Finn C, Spigel DR, Senan S, Langer C, Perez BA, Ozguroglu M, Daniel D, Villegas A, Vicente D, Hui R, Murakami S, Paz-Ares L, Broadhurst H, Wadsworth C, Dennis PA, Antonia SJ. Impact of prior chemoradiotherapy-related variables on outcomes with durvalumab in unresectable Stage III NSCLC (PACIFIC). Lung Cancer. 2021 Jan;151:30-38. doi: 10.1016/j.lungcan.2020.11.024. Epub 2020 Nov 26.
- Paz-Ares L, Spira A, Raben D, Planchard D, Cho BC, Ozguroglu M, Daniel D, Villegas A, Vicente D, Hui R, Murakami S, Spigel D, Senan S, Langer CJ, Perez BA, Boothman AM, Broadhurst H, Wadsworth C, Dennis PA, Antonia SJ, Faivre-Finn C. Outcomes with durvalumab by tumour PD-L1 expression in unresectable, stage III non-small-cell lung cancer in the PACIFIC trial. Ann Oncol. 2020 Jun;31(6):798-806. doi: 10.1016/j.annonc.2020.03.287. Epub 2020 Mar 21.
- 2014. "A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02125461.
Frequently Asked Questions
Are there other ongoing trials using MEDI4736?
"As of now, there are 338 ongoing clinical trials investigating MEDI4736. Out of those, 51 have reached Phase 3. MEDI4736 is being studied mostly in Wakayama-shi and Texas, but there are 12902 total locations running trials for this medication." - Anonymous Online Contributor
Unverified Answer
Are there any conditions that would make a person ineligible to participate in this research?
"This study is testing a new cancer medication and is only open to patients with non-small-cell lung carcinoma between the ages of 18 and 130. A total of 713 people can take part in this clinical trial." - Anonymous Online Contributor
Unverified Answer
Does this research project only allow young people, or are seniors also welcome to participate?
"This study is enrolling people who are older than 18 and younger than 130." - Anonymous Online Contributor
Unverified Answer
What are the recorded negative effects of MEDI4736?
"There is some evidence from earlier phases of testing as well as multiple rounds of safety testing that support the use of MEDI4736, so it received a score of 3." - Anonymous Online Contributor
Unverified Answer
What are the most popular MEDI4736 treatments?
"MEDI4736 is the most standard form of treatment for unresectable stage iii non-small cell lung cancer. However, this immunotherapy can also help patients with metastatic ureter urothelial carcinoma and advance directives." - Anonymous Online Contributor
Unverified Answer