Thyroid Cancer, Colon Cancer, Ovarian Cancer, Breast Cancer, Lung Cancer, Pancreatic Cancer
Conditions
Keywords
locally advanced or metastatic, carcinoembryonic antigen (CEA)-expressing, CEA, carcinoembryonic antigen
Brief summary
This is a phase 1b/2 study to evaluate the safety, tolerability, and efficacy of ETBX-011 vaccine used in combination with ALT-803 in subjects with locally advanced or metastatic CEA-expressing cancers whose tumor has recurred after standard-of-care treatment.
Detailed description
The trial will consist of a phase 1b study with ETBX-011 as a fixed dose with a dose escalation of ALT-803 unless de-escalation is required. The proposed phase 2 expansion study will give additional safety data for the MTD as well as preliminary efficacy data. Subjects will receive treatments unless they experience progressive disease, dose-limiting toxicities (DLT), withdraw consent, or if the investigator determines it is no longer in their best medical interest to continue treatment.
Interventions
BIOLOGICALETBX-011
ETBX-011 immunization was administered by subcutaneous (SC) injection.
BIOLOGICALALT-803
ALT-803 was administered by SC injection.
Sponsors
NantCell, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
ETBX-011 immunization was administered by subcutaneous (SC) injection. ALT-803 will be administered by SC injection.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age≥ 21 years. 2. Subjects with a histologically confirmed diagnosis of locally advanced or metastatic malignancy who were previously treated with at least one method of standard therapy known to have a possible survival benefit or refused such therapy. 3. The tumor must express CEA or must be known to be universally CEA positive (ie, colon and rectal cancer). 4. Must have a recent FFPE tumor biopsy specimen. 5. Subjects who have received prior CEA-targeted immunotherapy (eg, vaccine or antibody) are eligible for this trial if this treatment was discontinued at least 3 months prior to enrollment. 6. Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical procedures to NCI CTCAE grade ≤ 1. 7. Ability to understand and provide signed informed consent that fulfills Institutional Review Board (IRB)'s guidelines. 8. ECOG performance status of 0 or 1. 9. Subjects who are taking medications that do not have a known history of immunosuppression are eligible for this trial. 10. Adequate hematologic function at screening, as follows: 11. WBC count ≥ 3000/microliter. 12. Hemoglobin ≥ 9 g/dL (may not transfuse or use erythropoietin to achieve this level). 13. Platelets ≥ 75,000/microliter. 14. Prothrombin (PT)-international normalized ratio (INR) \< 1.5. 15. Partial thromboplastin time (PTT) \< 1.5 × upper limit of normal (ULN). 16. Adequate renal and hepatic function at screening, as follows: 17. Serum creatinine \< 2.0 mg/dL. 18. Bilirubin \< 1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL). 19. Alanine aminotransferase (ALT) ≤ 2.5 × ULN. 20. Aspartate aminotransferase (AST) ≤ 2.5 × ULN. 21. Female subjects of childbearing potential and women \< 12 months since the onset of menopause must agree to use acceptable contraceptive methods for the duration of the study and for 7 months following the last injection of study medication. Male subjects must be surgically sterile or must agree to use a condom and acceptable contraceptive method with their partner. 22. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
Exclusion criteria
1. Participation in an investigational drug or device study within 30 days of screening for this study. 2. Pregnant and nursing women. 3. Subjects with ongoing everolimus or other cancer therapy that interferes with the induction of immune responses. 4. Subjects with concurrent cytotoxic chemotherapy or radiation therapy. There must be at least one (1) month between any other prior chemotherapy (or radiotherapy) and study treatment. Any prior CEA-targeted immunotherapy (vaccine) must have been discontinued at least 3 months before initiation of study treatment. Subjects must have recovered from all acute toxicities from prior treatment prior to screening for this study. 5. Active brain or central nervous system metastasis, seizures requiring anticonvulsant treatment, cerebrovascular accident (\< 6 months), or transient ischemic attack. 6. Subjects with a history of autoimmune disease (active or past), such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune-related thyroid disease and vitiligo are permitted. 7. Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment. 8. Subjects with a history of heart disease, such as congestive heart failure (class II, III, or IV defined by the New York Heart Association functional classification), history of unstable or poorly controlled angina, or history (\< 1 year) of ventricular arrhythmia. 9. Subjects with a medical or psychological impediment that would impair the ability of the subject to receive therapy per protocol or impact ability to comply with the protocol or protocol-required visits and procedures. 10. History of malignancy except for the following: adequately treated non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, or other carcinoma that has been in complete remission without treatment for more than 5 years. 11. Presence of a known active acute or chronic infection, including human immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay \[ELISA\] and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV, as determined by HBsAg and hepatitis C serology). 12. Subjects on systemic intravenous or oral steroid therapy (or other immunosuppressives, such as azathioprine or cyclosporin A) are excluded on the basis of potential immune suppression. Subjects must have had at least 6 weeks of discontinuation of any steroid therapy (except that used as premedication for chemotherapy or contrast-enhanced studies) prior to enrollment. 13. Subjects with known allergy or hypersensitivity to any component of the investigational product will be excluded. 14. Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded. 15. Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist®) or a killed (inactivated)/subunit vaccine (e.g., PNEUMOVAX®, Fluzone®) within 28 days or 14 days, respectively, of the first planned dose of ETBX-011 or ALT 803.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Dose-Limiting Toxicities | 9 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Up to 11 weeks | The duration of overall response was measured from the time measurement criteria are met for CR or PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). |
| Progression Free Survival | Up to 11 weeks | PFS was defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurred first. Subjects who did not have disease progression or did not die at the end of follow up were to be censored at the last known date the subject was progression free. |
| Overall Survival | Up to 6 months | OS was evaluated by dose cohort and overall using the Kaplan-Meier method. OS was defined as the time from the date of first treatment to the date of death from any cause. Subjects who were alive at the end of follow up were to be censored at the last known date alive. |
Countries
United States
Participant flow
Pre-assignment details
Only the first dose level, N-803 10 μg/kg/dose + ETBX-011 (5 × 10\^11 VP/dose), was administered due to study termination. No additional escalations or the expansion phase (Phase 2) occurred. No patients had a response, therefore, Duration of Response could not be summarized. Only 2 out of 3 enrolled patients had a response assessment data, therefore, Progression Free Survival and Overall Survival analyses will not provide a meaningful result.
Participants by arm
| Arm | Count |
|---|---|
| ETBX-011 in Combination With ALT-803 A combination of agents were administered to subjects in this dose-escalation study
ETBX-011: ETBX-011 immunization was administered by subcutaneous (SC) injection.
ALT-803: ALT-803 was administered by SC injection. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | ETBX-011 in Combination With ALT-803 |
|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 7.57 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
| Subjects with previously treated locally advanced or metastatic CEA-expressing cancer | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Participants With Dose-Limiting Toxicities
Time frame: 9 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETBX-011 in Combination With ALT-803 | Number of Participants With Dose-Limiting Toxicities | 1 Participants |
Secondary
Duration of Response
The duration of overall response was measured from the time measurement criteria are met for CR or PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started).
Time frame: Up to 11 weeks
Population: No objective responses were observed.
Secondary
Overall Survival
OS was evaluated by dose cohort and overall using the Kaplan-Meier method. OS was defined as the time from the date of first treatment to the date of death from any cause. Subjects who were alive at the end of follow up were to be censored at the last known date alive.
Time frame: Up to 6 months
Population: No objective responses were observed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ETBX-011 in Combination With ALT-803 | Overall Survival | NA Months |
Secondary
Progression Free Survival
PFS was defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurred first. Subjects who did not have disease progression or did not die at the end of follow up were to be censored at the last known date the subject was progression free.
Time frame: Up to 11 weeks
Population: No objective responses were observed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETBX-011 in Combination With ALT-803 | Progression Free Survival | 3 Participants |