GastroEsophageal Cancer, Resectable Esophageal Cancer
Conditions
Brief summary
This is a 2 part Phase I/II clinical trial evaluating the safety, tolerability and efficacy of avelumab in combination with chemoradiation in patients with resectable esophageal and gastroesophageal cancer. Part 1: This is the run-in phase of the trial. This portion will determine the safety and tolerability of avelumab in combination with chemoradiotherapy in 6 patients. The proposed combination will be considered as safe if dose limiting toxicities are observed in at most 1 patient. Part 2: This is a Phase 2 portion of the trial, which will evaluate the efficacy of the proposed treatment regimen in patients with stage II/III resectable esophageal and gastroesophageal cancer
Detailed description
Background: Neoadjuvant chemoradiation is part of the standard of care for patients with stage II and III resectable esophageal and gastroesophageal cancer. This approach is based on the results of a large randomized clinical trial (CROSS) that demonstrated superior survival in patients receiving neoadjuvant chemoradiotherapy followed by surgical resection compared to patients treated with surgery alone. Pathological complete response at the time of resection is strongly linked to better survival. However, with current strategies pathological complete response is achieved only in a minority (29%) of patients. Remaining patients, especially those with positive lymph nodes at the time of the resection, are at significant risk for recurrences. Five-year survival rate for these patients is only 37%, and overall survival is as low as 9 months for those with persistent lymph node disease. Among patients who develop recurrent disease, most present with distant metastases outside of the radiation field. This is not surprising since the accepted treatment paradigm for this disease does not target possible disseminated microscopic systemic disease. Hence, novel strategies are needed to improve outcomes of these patients. We propose conducting a phase I/II clinical trial evaluating a role of immune checkpoint inhibitor in combination with chemoradiotherapy and post-operatively in the management of resectable esophageal cancer. Study Rationale: 1. A number of preclinical and clinical studies demonstrated synergism between radiation and immunotherapy, suggesting that combining these approaches can enhance anti-tumor activity and increase treatment efficacy. 2. Immune checkpoint inhibitors have demonstrated promising activity in a subset of patients with metastatic esophageal and gastric cancers. Moving these agents into neoadjuvant setting may increase the cure rate of this disease compared to the standard approach. 3. Current neoadjuvant therapy does not target any potential microscopic disease outside of the radiation field since chemotherapy serves primarily as a radiation sensitizer. Immunotherapy treatment will target both local and systemic disease. Hypothesis: We hypothesize that co-administration of avelumab with chemoradiation will be well tolerated and will increase pathological complete response rate in resected tumor specimens. We hypothesize that avelumab treatment will also decrease the rates of disease recurrence. Study Design: This is a 2 part Phase I/II clinical trial evaluating the safety, tolerability and efficacy of avelumab in combination with chemoradiation in patients with resectable esophageal and gastroesophageal cancer. Part 1: This is the run-in phase of the trial. This portion will determine the safety and tolerability of avelumab in combination with chemoradiotherapy in 6 patients. The proposed combination will be considered as safe if dose limiting toxicities are observed in at most 1 patient. Part 2: This is a Phase 2 portion of the trial, which will evaluate the efficacy of the proposed treatment regimen in patients with stage II/III resectable esophageal and gastroesophageal cancer. Objectives: Primary: Evaluate the safety of avelumab in combination with chemoradiation in patients with resectable esophageal cancer and gastroesophageal receiving perioperative therapy. Secondary: Obtain efficacy data and further safety data of the proposed drug combination in this patient population. Exploratory objectives: The translational focus of the study will evaluate changes in tumor microenvironment that occur in response to radiation and immunotherapy. Endpoints: Part 1 - Primary endpoint: Establish safety and tolerability of the proposed treatment. Part 2 - Primary Endpoint: Pathological complete response rate. Part 2 - Secondary Endpoints: 1. Safety and tolerability. 2. Disease free survival. 3. Incidence of surgical complications. 4. Rate of R0 resection. Number of centers & patients: One center. Part 1: total of 6 eligible patients will be accrued to evaluate the safety and tolerability of the proposed combination. Part 2: 18 patients will be enrolled in the phase 2 portion of the trial. Population: Patients with histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus and gastroesophagus who are candidates for neoadjuvant therapy and surgical resection. Investigational drugs: Avelumab (Provided by EMD Serono). IND information to be added as needed.
Interventions
COMBINATION_PRODUCTAvelumab combined with Chemoradiation
Co-administration of avelumab with chemoradiation in pre-operative period.
DRUGCarboplatin
Weekly Carboplatin (AUC2) \[intravenous infusion on days 1, 8, 15, 22, & 29\]
DRUGPaclitaxel
Weekly paclitaxel \[intravenous infusion on days 1, 8, 15, 22, & 29\]
RADIATIONRadiation
Radiation therapy \[23 fractions, M-F, estimated completion day 35\]
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study is a two-part phase 1/2 clinical trial conducted in one center. Part 1. Run-in phase to assess the safety and tolerability of avelumab in combination with chemoradiation. Will enroll 6 patients, after which accrual will be stopped temporarily while safety data is being obtained. Part 2. An open-label phase 2 study. Part 2 will obtain further safety data of the proposed drug combination and will evaluate the anti-tumor efficacy of perioperative avelumab and chemoradiation in this patient population. Will enroll 18 additional patients. Each phase of the study will have a 21-day screening period, treatment procedures (neoadjuvant therapy, resection and adjuvant therapy), and active surveillance for a year after the completion of adjuvant therapy. After active surveillance visit at 12 months post treatment completion, survival data and disease status will be collected via phone calls or medical record review every 6 months during the following 3 years.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus and gastroesophagus (Siewert type 1-3) 2. Locoregional disease with clinical stage of T1N1 or T2-3N0-2 3. No clinical evidence of metastatic spread. Staging should include endoscopic ultrasound and positron emission tomography/computed tomography (PET/CT) as recommended by National Comprehensive Cancer Network (NCCN) guidelines. PET/CT should be performed within 3 weeks of signing informed consent 4. Age 18 years or older 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 6. Subjects must be deemed to be potential surgical candidates by an evaluating surgeon 7. Adequate organ function: 1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 2. Hemoglobin ≥ 9 g/dL (transfusions allowed) 3. Platelets ≥ 100 x 109/L 4. Aspartate transaminase/Alanine transaminase (AST/ALT) ≤ 2.5 x ULN 5. Total serum bilirubin of ≤1.5 x institutional upper limit of normal (ULN) 6. Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula 8. Female patients of childbearing potential must have a negative pregnancy test (urine or serum) within 21 days prior to the start of the study drug treatment and must agree to use adequate birth control if conception is possible during the study and up to 30 days after the completion of adjuvant therapy 9. Male patients must agree to use adequate birth control during the study and up to 30 days after the last avelumab dose 10. Women who are nursing must discontinue breast-feeding prior to the enrollment in the trial 11. Patient must be able and willing to comply with study procedures as per protocol 12. Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures
Exclusion criteria
1. Prior history of radiation to the mediastinum 2. Diagnosis of cervical esophageal carcinoma 3. Other active malignancy within the last 3 years (except for non-melanoma skin cancer, a non-invasive/in situ cancer, or indolent non metastatic Gleason 6 prostate cancer) 4. Subjects with an active or known autoimmune disease. Subjects with type I diabetes mellitus, hypo- or hyperthyroidism only requiring hormone replacement/suppression, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic immunosuppressive treatment are eligible 5. Current use of immunosuppressive medication, except for the following: 1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) 2. systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent 3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 6. Active infection requiring systemic therapy at the time of study treatment initiation 7. Prior organ transplantation including allogenic stem-cell transplantation 8. Known history of testing positive for HIV or known immunodeficiency syndrome 9. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive) 10. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines 11. Major surgery within prior 4 weeks of treatment initiation (the surgical incision should be fully healed prior to all neoadjuvant treatment initiation) 12. Any prior anticancer therapy for esophageal cancer 13. History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel or avelumab, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3) 14. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. Patients with stable rate-controlled atrial fibrillation will be allowed to participate 15. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study 16. Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity | Up to 4 weeks post-resection (up to approximately 4 months on study) of all Run-In Phase participants | 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. |
| Number of Participants With Pathological Complete Response | Post-resection (80-100 days) pathology review for all participants (up to approximately 4 months on study) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Unexpected Surgical Complications | Following resection (80 -100 days) for all participants (up to approximately 5 months on study) | — |
| Rate of R0 Resection | Following pathology review post-resection (80 -100 days) for all participants (up to approximately 4 months on study) | R0 resection corresponds to resection for cure or complete remission. |
| Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | 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). |
| Estimated 1-year Recurrence Free Survival | up to 1 year | — |
| Disease Free Survival | Up to 4 years post-resection for all participants | 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. |
| Number of Participants Who Did or Did Not Complete Planned Treatment | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the University of Wisconsin Hospital and Clinics from May 2018 through June 2021.
Participants by arm
| Arm | Count |
|---|---|
| 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 \[23 fractions, M-F, estimated completion day 35\]. | 6 |
| 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). | 16 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 1 Year Follow Up Post Last Dose | Death | 1 | 1 |
| Treatment: Expansion (Feb 2019-Dec 2021) | Adverse Event | 0 | 2 |
| Treatment: Expansion (Feb 2019-Dec 2021) | Death | 0 | 1 |
| Treatment: Expansion (Feb 2019-Dec 2021) | Off Treatment Post-Surgery | 0 | 2 |
| Treatment: Expansion (Feb 2019-Dec 2021) | Off Treatment Pre-Surgery | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Expansion Cohort | Run-In Phase |
|---|---|---|---|
| Age, Customized 40-49 years | 2 Participants | 2 Participants | 0 Participants |
| Age, Customized 50-59 years | 4 Participants | 2 Participants | 2 Participants |
| Age, Customized 60-69 years | 8 Participants | 5 Participants | 3 Participants |
| Age, Customized 70-79 years | 8 Participants | 7 Participants | 1 Participants |
| ECOG Performance Status 0 - Fully active, able to carry on all pre-disease performance without restriction | 12 Participants | 8 Participants | 4 Participants |
| ECOG Performance Status 1 - Restricted in strenuous activity, ambulatory, able to carry out light or sedentary work | 10 Participants | 8 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 15 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Histology Adenocarcinoma | 19 Participants | 13 Participants | 6 Participants |
| Histology Squamous | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 16 Participants | 6 Participants |
| Region of Enrollment United States | 22 participants | 16 participants | 6 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 14 Participants | 6 Participants |
| Tumor Location Esophageal | 8 Participants | 8 Participants | 0 Participants |
| Tumor Location Gastroesophageal Junction | 14 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 6 | 6 / 16 |
| other Total, other adverse events | 6 / 6 | 16 / 16 |
| serious Total, serious adverse events | 3 / 6 | 10 / 16 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicity
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.
Time frame: Up to 4 weeks post-resection (up to approximately 4 months on study) of all Run-In Phase participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Run-In Phase | Number of Participants With Dose Limiting Toxicity | 0 Participants |
Primary
Number of Participants With Pathological Complete Response
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.
Time frame: Post-resection (80-100 days) pathology review for all participants (up to approximately 4 months on study)
Population: 3 participants did not have surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Run-In Phase | Number of Participants With Pathological Complete Response | 2 Participants |
| Expansion Cohort | Number of Participants With Pathological Complete Response | 3 Participants |
Secondary
Disease Free Survival
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Run-In Phase | Disease Free Survival | NA days |
Secondary
Estimated 1-year Recurrence Free Survival
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Run-In Phase | Estimated 1-year Recurrence Free Survival | 71 percentage of participants |
Secondary
Number of Participants Who Did or Did Not Complete Planned Treatment
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.
Time frame: Up to 30 days post-avelumab of all participants (up to 4 months on study)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Run-In Phase | Number of Participants Who Did or Did Not Complete Planned Treatment | Completed All Protocol Treatment | 6 Participants |
| Run-In Phase | Number of Participants Who Did or Did Not Complete Planned Treatment | Completed Neoadjuvant Therapy and Planned Surgical Resection | 6 Participants |
| Run-In Phase | Number of Participants Who Did or Did Not Complete Planned Treatment | Did not complete all planned Neoadjuvant Treatment | 0 Participants |
| Expansion Cohort | Number of Participants Who Did or Did Not Complete Planned Treatment | Completed All Protocol Treatment | 13 Participants |
| Expansion Cohort | Number of Participants Who Did or Did Not Complete Planned Treatment | Completed Neoadjuvant Therapy and Planned Surgical Resection | 10 Participants |
| Expansion Cohort | Number of Participants Who Did or Did Not Complete Planned Treatment | Did not complete all planned Neoadjuvant Treatment | 3 Participants |
Secondary
Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3
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).
Time frame: Up to 30 days post-avelumab of all (up to 4 months on study)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Lymphopenia | 5 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | White Blood Cell Decrease | 4 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Neutropenia | 2 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Diarrhea | 0 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Acute Kidney Injury | 0 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Hypotension | 0 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Dehydration | 1 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Infusion Reaction | 0 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Nausea | 1 Participants |
| Run-In Phase | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Hypersensitivity Reaction to Avelumab | 0 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Infusion Reaction | 1 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Lymphopenia | 16 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Hypotension | 1 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | White Blood Cell Decrease | 9 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Hypersensitivity Reaction to Avelumab | 1 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Neutropenia | 4 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Dehydration | 0 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Diarrhea | 1 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Nausea | 0 Participants |
| Expansion Cohort | Number of Participants With Treatment Related Adverse Events Greater Than or Equal to Grade 3 | Acute Kidney Injury | 1 Participants |
Secondary
Number of Participants With Unexpected Surgical Complications
Time frame: Following resection (80 -100 days) for all participants (up to approximately 5 months on study)
Population: 3 participants did not undergo resection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Run-In Phase | Number of Participants With Unexpected Surgical Complications | 0 Participants |
| Expansion Cohort | Number of Participants With Unexpected Surgical Complications | 0 Participants |
Secondary
Rate of R0 Resection
R0 resection corresponds to resection for cure or complete remission.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Run-In Phase | Rate of R0 Resection | 5 Participants |
| Expansion Cohort | Rate of R0 Resection | 10 Participants |