Tremelimumab and Durvalumab With or Without Radiation Therapy in Patients With Relapsed Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT02701400
• Recruitment Status: Completed
• First Posted: March 8, 2016
• Results First Posted: June 22, 2021
• Last Update Posted: June 22, 2021
• Sponsor: Emory University
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Taofeek K. Owonikoko, Emory University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent Small Cell Lung Carcinoma
• Interventions: Biological: Durvalumab; Radiation: Hypofractionated Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy; Biological: Tremelimumab
• Enrollment: 18

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
Arm/Group Description	Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation. Durvalumab: Given IV Tremelimumab: Given IV	Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I. Durvalumab: Given IV Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Stereotactic Body Radiation Therapy: Undergo SBRT Tremelimumab: Given IV
Period Title: Overall Study
Started	9	9
Completed	9	9
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)	Total
Arm/Group Description		Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation. Durvalumab: Given IV Tremelimumab: Given IV	Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I. Durvalumab: Given IV Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Stereotactic Body Radiation Therapy: Undergo SBRT Tremelimumab: Given IV	Total of all reporting groups
Overall Number of Baseline Participants		9	9	18
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9 participants	9 participants	18 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	4 44.4%	4 44.4%	8 44.4%
	>=65 years	5 55.6%	5 55.6%	10 55.6%
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	9 participants	9 participants	18 participants
		70.5 [2] (NA)	66.86 [2] (NA)	67.76 [2] (NA)
		[1] Measure Description: The measure of dispersion data are not available. All efforts were made to obtain these data from the PI and the study documentation.; [2] There is no standard deviation for this trial
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9 participants	9 participants	18 participants
	Female	3 33.3%	4 44.4%	7 38.9%
	Male	6 66.7%	5 55.6%	11 61.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9 participants	9 participants	18 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	9 100.0%	9 100.0%	18 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9 participants	9 participants	18 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 11.1%	1 5.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	3 33.3%	3 16.7%
	White	8 88.9%	5 55.6%	13 72.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 11.1%	0 0.0%	1 5.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	9 participants	9 participants	18 participants
		9	9	18

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Time from initiation of therapy to objective disease progress or death
Time Frame	From initiation of systemic therapy to first documented disease progression, assessed through study completion, up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
Arm/Group Description:	Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation. Durvalumab: Given IV Tremelimumab: Given IV	Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I. Durvalumab: Given IV Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Stereotactic Body Radiation Therapy: Undergo SBRT Tremelimumab: Given IV
Overall Number of Participants Analyzed	9	9
Median (Standard Deviation); Unit of Measure: months
	2.1 (0)	3.3 (28.6)

2. Primary Outcome

Title	Objective Response Rate
Description	Disease response to therapy measured according to RECIST 1.1 criteria
Time Frame	After every 2 cycles of treatment (1 cycle = 4 weeks), assessed through study completion, up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
Arm/Group Description:	Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation. Durvalumab: Given IV Tremelimumab: Given IV	Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I. Durvalumab: Given IV Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Stereotactic Body Radiation Therapy: Undergo SBRT Tremelimumab: Given IV
Overall Number of Participants Analyzed	9	9
Median (Standard Deviation); Unit of Measure: months
	2.76 (3.9)	2.76 (3.9)

3. Secondary Outcome

Title	Immune-related Objective Response Rate
Description	Disease response to treatment using immune-related response rate (irRR) criteria
Time Frame	Assessed after every 2 cycles (1 cycle = 4 weeks) on treatment; assessed through study completion, up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
Arm/Group Description:	Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation. Durvalumab: Given IV Tremelimumab: Given IV	Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I. Durvalumab: Given IV Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Stereotactic Body Radiation Therapy: Undergo SBRT Tremelimumab: Given IV
Overall Number of Participants Analyzed	9	9
Measure Type: Count of Participants; Unit of Measure: Participants
	9 100.0%	9 100.0%

4. Secondary Outcome

Title	Overall Survival
Description	Time interval from entering the study until death
Time Frame	From randomization until death from any cause, assessed through study completion, up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
Arm/Group Description:	Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation. Durvalumab: Given IV Tremelimumab: Given IV	Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I. Durvalumab: Given IV Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Stereotactic Body Radiation Therapy: Undergo SBRT Tremelimumab: Given IV
Overall Number of Participants Analyzed	9	9
Median (95% Confidence Interval); Unit of Measure: months
	2.8; (0.8 to 12.4)	5.7; (1.6 to 14.5)

5. Other Pre-specified Outcome

Title	Change From Baseline in the Proportion of Lymphocyte Subset (CD8+ICOS+) Between Baseline and On-Treament (End of Cycle 1)
Description	Change in circulating and tumor-infiltrating lymphocytes between baseline and on-treatment samples at the end of Cycle 1. The proportion was calculated as the number of specific lymphocytes subset out of the total number of lymphocytes at baseline compared to the same proportion at the end of cycle 1.
Time Frame	Result presented for assessment at baseline and the end of cycle 1.

Outcome Measure Data

Analysis Population Description

All patients with at least 2 paired samples collected at baseline and on-treatment at end of cycle 1

Arm/Group Title	Pooled Analysis (Arms I and II)
Arm/Group Description:	Durvalumab: Given IV Tremelimumab: Given IV Patients in Arm II undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I.
Overall Number of Participants Analyzed	8
Overall Number of Units Analyzed; Type of Units Analyzed: Lymphocyte subtypes	13
Mean (95% Confidence Interval); Unit of Measure: proportion of CD8+ICOS+ Tcells
	1.399; (0.03091 to 2.766)

Adverse Events

Time Frame	Adverse events collected through study completion, up to 2 years.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
Arm/Group Description	Patients receive tremelimumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive durvalumab IV over 1 hour on day 1. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving disease control may restart treatment upon evidence of progressive disease, with or without confirmation. Durvalumab: Given IV Tremelimumab: Given IV	Patients undergo stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy daily for 5 days over 1 week or for 3 fractions every other day for 1 week and then receive the same treatment as in Arm I. Durvalumab: Given IV Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy Stereotactic Body Radiation Therapy: Undergo SBRT Tremelimumab: Given IV
All-Cause Mortality
	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	9/9 (100.00%)	8/9 (88.89%)
Serious Adverse Events
	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/9 (0.00%)	0/9 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm I (Tremelimumab, Durvalumab)	Arm II (RT, Tremelimumab, Durvalumab)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/9 (0.00%)	0/9 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Taofeek Owonikoko
• Organization: Emory University
• Phone: 404-778-5575
• EMail: TOWONIK@emory.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pakkala S, Higgins K, Chen Z, Sica G, Steuer C, Zhang C, Zhang G, Wang S, Hossain MS, Nazha B, Beardslee T, Khuri FR, Curran W, Lonial S, Waller EK, Ramalingam S, Owonikoko TK. Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study. J Immunother Cancer. 2020 Dec;8(2):e001302. doi: 10.1136/jitc-2020-001302.

• Responsible Party: Taofeek K. Owonikoko, Emory University
• ClinicalTrials.gov Identifier: NCT02701400
• Other Study ID Numbers: IRB00086004; NCI-2016-00026 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); ESR-14-10531 ( Other Identifier: AstraZeneca ); Winship3112-15 ( Other Identifier: Emory University/Winship Cancer Institute )
• First Submitted: February 23, 2016
• First Posted: March 8, 2016
• Results First Submitted: November 5, 2020
• Results First Posted: June 22, 2021
• Last Update Posted: June 22, 2021