Trial Outcomes & Findings for Study of Pembrolizumab in Locally Advanced Esophageal Adenocarcinoma (NCT NCT02998268)

Last Updated: 2025-03-19

Results Overview

Tumor tissue will be assessed for major pathological response as defined as complete response or near complete response. Pathologic response was assessed by tumor regression grade. This is a pathologic assessment of the amount of residual cancer cells in the specimen and the degree of fibrosis in the sample specimen. A completer response is 0% residual cancer cells. A partial response is 10-50% residual cancer cells, and no response is \>50% residual cancer cells within the tumor specimen.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Between approximately week 15 to 19

Results posted on

2025-03-19

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1 Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Cohort 2 Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.
Overall Study STARTED	20	22
Overall Study COMPLETED	20	19
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Cohort 2 Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.
Overall Study Adverse Event	0	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Study of Pembrolizumab in Locally Advanced Esophageal Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=20 Participants Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Cohort 2 n=22 Participants Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Total n=42 Participants Total of all reporting groups
Age, Continuous	61.87 years n=5 Participants	67.38 years n=7 Participants	65.06 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	2 Participants n=5 Participants	0 Participants n=7 Participants	2 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	18 Participants n=5 Participants	21 Participants n=7 Participants	39 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants

PRIMARY outcome

Timeframe: Between approximately week 15 to 19

Population: 3 participants in Cohort 2 did not have surgery and were therefore ineligible.

Outcome measures

Outcome measures
Measure	Cohort 1 n=20 Participants Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Cohort 2 n=19 Participants Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.
Number of Participants With Major Pathological Response	9 Participants	10 Participants

SECONDARY outcome

Timeframe: 1 year

Population: 1 participant in Cohort 1 and 3 participants in Cohort 2 were unevaluable.

To examine the efficacy of the combination of pembrolizumab with chemotherapy and chemoradiation as assessed by R0 resection rate, which is reported as the number of participants achieving R0 resection.

Outcome measures

Outcome measures
Measure	Cohort 1 n=19 Participants Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Cohort 2 n=19 Participants Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.
R0 Resection Rate.	17 Participants	16 Participants

SECONDARY outcome

Timeframe: Until death from any cause or for a maximum of 5 years

To examine the efficacy of the combination of pembrolizumab with chemotherapy and chemoradiation as assessed by overall survival rates

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: 3 participants in Cohort 2 were unevaluable

Number of participants that remained progression free (per RECIST v1.1) and alive as of 1 year

Outcome measures

Outcome measures
Measure	Cohort 1 n=20 Participants Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Cohort 2 n=19 Participants Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.
Number of Participants That Remained Progression Free as of 1 Year	15 Participants	12 Participants

Adverse Events

Cohort 1

Serious events: 8 serious events

Other events: 20 other events

Deaths: 7 deaths

Cohort 2

Serious events: 13 serious events

Other events: 22 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Manish Shah

Weill Cornell Medicine

Phone: 646-962-6200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Cohort 1 n=20 participants at risk Subjects in Cohort 1 receive conventional induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.	Cohort 2 n=22 participants at risk Subjects in Cohort 2 receive pembrolizumab along with induction chemotherapy with taxol/ carboplatin followed by weekly chemoradiation (taxol/ carboplatin) with pembrolizumab. Following surgery, pembrolizumab is administered every 3 weeks for 1 year. Pembrolizumab dosing is 200 mg administered as a 30 minute IV infusion. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Taxol: Taxol is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Carboplatin: Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. Carboplatin produces predominantly interstrand DNA cross-links rather than DNA -protein cross-links.
Blood and lymphatic system disorders Anemia	30.0% 6/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	40.9% 9/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Metabolism and nutrition disorders Anorexia	60.0% 12/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	50.0% 11/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Psychiatric disorders Anxiety	15.0% 3/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	27.3% 6/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Abdominal distension	20.0% 4/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	0.00% 0/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Abdominal pain	80.0% 16/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	31.8% 7/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Investigations Alanine Aminotransferase Increased	25.0% 5/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	13.6% 3/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Investigations Alkaline Phosphatase Increased	15.0% 3/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	9.1% 2/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Skin and subcutaneous tissue disorders Alopecia	70.0% 14/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	59.1% 13/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Musculoskeletal and connective tissue disorders Arthralgia	35.0% 7/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	40.9% 9/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Investigations Aspartate aminotransferase increased	25.0% 5/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	4.5% 1/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Cardiac disorders Asystole	0.00% 0/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	4.5% 1/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Musculoskeletal and connective tissue disorders Back Pain	20.0% 4/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	13.6% 3/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Bloating	5.0% 1/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	13.6% 3/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
General disorders Chills	10.0% 2/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	4.5% 1/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Respiratory, thoracic and mediastinal disorders Chylothorax	5.0% 1/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	9.1% 2/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Constipation	60.0% 12/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	45.5% 10/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Respiratory, thoracic and mediastinal disorders Cough	35.0% 7/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	54.5% 12/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Investigations Creatinine Increased	10.0% 2/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	4.5% 1/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Metabolism and nutrition disorders Dehydration	10.0% 2/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	31.8% 7/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Psychiatric disorders Depression	10.0% 2/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	13.6% 3/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Diarrhea	30.0% 6/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	31.8% 7/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
General disorders Dizziness	15.0% 3/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	13.6% 3/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Dry Skin	15.0% 3/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	4.5% 1/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Dry mouth	10.0% 2/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	4.5% 1/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Dyspepsia	5.0% 1/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	54.5% 12/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Dysphagia	75.0% 15/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	68.2% 15/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Respiratory, thoracic and mediastinal disorders Dyspnea	40.0% 8/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	54.5% 12/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Infections and infestations Enterocolitis infectious	10.0% 2/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	0.00% 0/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Skin and subcutaneous tissue disorders Erythema multiforme	15.0% 3/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	22.7% 5/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Injury, poisoning and procedural complications Esophageal Anastomotic Leak	5.0% 1/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	22.7% 5/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Esophagitis	30.0% 6/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	27.3% 6/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
General disorders Fatigue	95.0% 19/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	81.8% 18/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
General disorders Fever	20.0% 4/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	9.1% 2/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
General disorders Gait disturbance	0.00% 0/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	9.1% 2/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Gastrointestinal disorders Gastroesophageal reflux disease	55.0% 11/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	0.00% 0/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
General disorders Generalized muscle weakness	55.0% 11/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	27.3% 6/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Nervous system disorders Headache	5.0% 1/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	9.1% 2/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Renal and urinary disorders Hematuria	10.0% 2/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	0.00% 0/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Metabolism and nutrition disorders Hyperglycemia	5.0% 1/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	9.1% 2/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/20 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.	9.1% 2/22 • Adverse events (AEs) were collected for a maximum of 30 days from the last dose of study drug administration. The maximum length of time that a participant was followed for AEs is approximately 25 months. Participants are being followed for overall survival for up to 5 years, so mortality data collection is ongoing.