Trial Outcomes & Findings for Avelumab With Chemoradiation for Stage II/III Resectable Esophageal and Gastroesophageal Cancer (NCT NCT03490292)

Last Updated: 2024-07-26

Results Overview

A total number of 6 subjects will be enrolled during the run-in phase of the trial. A sample size of 6 is sufficient to estimate the true dose limiting toxicity rate of the proposed avelumab/chemoradiation therapy with adequate accuracy.The proposed treatment combination will be considered as safe if dose limiting toxicities are observed in at most 1 patient.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Up to 4 weeks post-resection (up to approximately 4 months on study) of all Run-In Phase participants

Results posted on

2024-07-26

Participant Flow

Participants were recruited from the University of Wisconsin Hospital and Clinics from May 2018 through June 2021.

Participant milestones

Participant milestones
Measure	Run In Phase 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a dose-limiting toxicity (DLT) during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation). Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]
Treatment: Run-In Phase (June-Oct 2018) STARTED	6	0
Treatment: Run-In Phase (June-Oct 2018) COMPLETED	6	0
Treatment: Run-In Phase (June-Oct 2018) NOT COMPLETED	0	0
Interim Analysis STARTED	6	0
Interim Analysis COMPLETED	6	0
Interim Analysis NOT COMPLETED	0	0
Treatment: Expansion (Feb 2019-Dec 2021) STARTED	0	16
Treatment: Expansion (Feb 2019-Dec 2021) COMPLETED	0	9
Treatment: Expansion (Feb 2019-Dec 2021) NOT COMPLETED	0	7
1 Year Follow Up Post Last Dose STARTED	6	9
1 Year Follow Up Post Last Dose COMPLETED	5	8
1 Year Follow Up Post Last Dose NOT COMPLETED	1	1
Survival Follow up 4 Yr Post Last Dose STARTED	5	8
Survival Follow up 4 Yr Post Last Dose COMPLETED	5	8
Survival Follow up 4 Yr Post Last Dose NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Run In Phase 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a dose-limiting toxicity (DLT) during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation). Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]
Treatment: Expansion (Feb 2019-Dec 2021) Death	0	1
Treatment: Expansion (Feb 2019-Dec 2021) Off Treatment Pre-Surgery	0	2
Treatment: Expansion (Feb 2019-Dec 2021) Off Treatment Post-Surgery	0	2
Treatment: Expansion (Feb 2019-Dec 2021) Adverse Event	0	2
1 Year Follow Up Post Last Dose Death	1	1

Baseline Characteristics

Avelumab With Chemoradiation for Stage II/III Resectable Esophageal and Gastroesophageal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Run-In Phase n=6 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\].	Expansion Cohort n=16 Participants Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).	Total n=22 Participants Total of all reporting groups
Age, Customized 40-49 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Customized 50-59 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Customized 60-69 years	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Age, Customized 70-79 years	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	15 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	16 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	16 participants n=7 Participants	22 participants n=5 Participants
Tumor Location Esophageal	0 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants
Tumor Location Gastroesophageal Junction	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Histology Squamous	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Histology Adenocarcinoma	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
ECOG Performance Status 0 - Fully active, able to carry on all pre-disease performance without restriction	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
ECOG Performance Status 1 - Restricted in strenuous activity, ambulatory, able to carry out light or sedentary work	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 weeks post-resection (up to approximately 4 months on study) of all Run-In Phase participants

Outcome measures

Outcome measures
Measure	Run-In Phase n=6 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Number of Participants With Dose Limiting Toxicity	0 Participants	—

PRIMARY outcome

Timeframe: Post-resection (80-100 days) pathology review for all participants (up to approximately 4 months on study)

Population: 3 participants did not have surgery.

Pathologic compete response (pCR) is defined as an absence of any viable tumor at microscopic examination of the primary tumor and any lymph nodes sampled after surgery following neoadjuvant therapy. Participants with invalid/missing pCR assessments will be defined as non-responders. The number and frequency of patients with a pCR will be summarized in tabular format.

Outcome measures

Outcome measures
Measure	Run-In Phase n=6 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort n=16 Participants Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Number of Participants With Pathological Complete Response	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 30 days post-avelumab of all (up to 4 months on study)

Part 2 will further evaluate the safety of the studied drug combination, building on the observations from Part 1. All patients who receive at least one dose of avelumab will be evaluated for toxicity. Toxicities observed will be summarized in terms of types and severities by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 (see Adverse Events section).

Outcome measures

Outcome measures
Measure	Run-In Phase n=6 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort n=16 Participants Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Lymphopenia	5 Participants	16 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 White Blood Cell Decrease	4 Participants	9 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Neutropenia	2 Participants	4 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Diarrhea	0 Participants	1 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Acute Kidney Injury	0 Participants	1 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Hypotension	0 Participants	1 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Dehydration	1 Participants	0 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Infusion Reaction	0 Participants	1 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Nausea	1 Participants	0 Participants
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 Hypersensitivity Reaction to Avelumab	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 30 days post-avelumab of all participants (up to 4 months on study)

Part 2 will further evaluate the tolerability of the studied drug combination, building on the observations from Part 1. Tolerability will be reported as the number of subjects who did or did not complete the planned treatment, including the reason they ended treatment early.

Outcome measures

Outcome measures
Measure	Run-In Phase n=6 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort n=16 Participants Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Number of Participants Who Did or Did Not Complete Planned Treatment Completed All Protocol Treatment	6 Participants	13 Participants
Number of Participants Who Did or Did Not Complete Planned Treatment Completed Neoadjuvant Therapy and Planned Surgical Resection	6 Participants	10 Participants
Number of Participants Who Did or Did Not Complete Planned Treatment Did not complete all planned Neoadjuvant Treatment	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Following resection (80 -100 days) for all participants (up to approximately 5 months on study)

Population: 3 participants did not undergo resection

Outcome measures

Outcome measures
Measure	Run-In Phase n=6 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort n=13 Participants Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Number of Participants With Unexpected Surgical Complications	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Following pathology review post-resection (80 -100 days) for all participants (up to approximately 4 months on study)

Population: 3 participants did not have surgery.

R0 resection corresponds to resection for cure or complete remission.

Outcome measures

Outcome measures
Measure	Run-In Phase n=6 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort n=13 Participants Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Rate of R0 Resection	5 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to 4 years post-resection for all participants

Population: median disease free survival was not reached by data cut-off on 7/13/2023, 1-year estimated Kaplan-Meier RFS was determined and reported in a separate outcome measure, all participants received the same intervention and are reported as a single group

Disease free survival (DFS) will be defined as the number of days from the day of resection to the day a subject experiences an event of disease recurrence or death, whichever comes first. If a subject has not experienced an event of disease recurrence progression or death at the time of analysis, then the subject's data will be censored at the date of the last available evaluation. DFS will be summarized using point estimates of the median time to progression and the associated 95% confidence interval. The data will be presented graphically using Kaplan-Meier plots.

Outcome measures

Outcome measures
Measure	Run-In Phase n=22 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Disease Free Survival	NA days median disease free survival was not reached by data cut-off on 7/13/2023, 1-year estimated Kaplan-Meier RFS was determined	—

SECONDARY outcome

Timeframe: up to 1 year

Population: 17 participants were evaluable for response assessment, all participants received the same intervention and are reported as a single group

Outcome measures

Outcome measures
Measure	Run-In Phase n=17 Participants 6 patients enrolled will receive weekly carboplatin (AUC2) and paclitaxel (50 mg/m2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] while undergoing radiation therapy \[23 fractions, M-F, estimated completion day 35\]. Avelumab combined with Chemoradiation - Avelumab (10 mg/kg IV) every 2 weeks starting on the day of the last chemotherapy infusion (day 29). A total of 3 doses administered during the pre-operative period and an additional 6 doses of avelumab post-operatively. Trial enrollment will resume after at least 5 patients do not have a DLT during the DLT evaluation period or until all 6 patients are seen for post-operative evaluation. If 2 or more patients experience dose limiting toxicities associated with the proposed treatments, further accrual of the subjects will be halted and trial will be suspended. Trial may be reopened in the future with appropriate schedule and dose modifications of the proposed treatment. Avelumab combined with Chemoradiation: Co-administration of avelumab with chemoradiation in pre-operative period. Carboplatin: Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Paclitaxel: Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, \& 29\] Radiation: Radiation therapy \[23 fractions, M-F, estimated completion day 35\]	Expansion Cohort Following a determination of safe and tolerable treatment outcome of the Run-In Phase, Part 2 of the trial will enroll up to 18 additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Estimated 1-year Recurrence Free Survival	71 percentage of participants Interval 43.0 to 87.0	—

Adverse Events

Run In Phase

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

Expansion Cohort

Serious events: 10 serious events

Other events: 16 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Nataliya Uboha, MD, PhD

UW Carbone Cancer Center

Phone: (608) 265-9966

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Run In Phase n=6 participants at risk Determination of safe and tolerable treatment outcome (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).	Expansion Cohort n=16 participants at risk Additional patients to evaluate activity of the proposed treatment and to obtain further safety information (carboplatin, paclitaxel, radiation \& Avelumab combined with Chemoradiation).
Gastrointestinal disorders Esophageal leak	16.7% 1/6 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	0.00% 0/16 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Gastrointestinal disorders Constipation	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Gastrointestinal disorders Esophageal fistula	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Gastrointestinal disorders Nausea	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
General disorders Fever	16.7% 1/6 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	12.5% 2/16 • Number of events 3 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Infections and infestations Enterocolitis infectious	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Infections and infestations Sepsis	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Infections and infestations Urinary tract infection	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Infections and infestations Wound infection	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	12.5% 2/16 • Number of events 2 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Investigations Weight loss	16.7% 1/6 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	0.00% 0/16 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	0.00% 0/16 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Psychiatric disorders Confusion	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	12.5% 2/16 • Number of events 3 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Respiratory, thoracic and mediastinal disorders Tachypnea	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Gastrointestinal disorders Jejunal obstruction	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Vascular disorders Hypotension	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Injury, poisoning and procedural complications Accidental J-tube removal	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Gastrointestinal disorders Colonic Ischemia	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.
Injury, poisoning and procedural complications Infusion Related Reaction	0.00% 0/6 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.	6.2% 1/16 • Number of events 1 • up to 4 weeks post resection (up to 4 months on study), survival data collected up to 4 years Participants in the Run-In Phase and the Expansion Cohort received the same treatment.