Non-small Cell Lung Cancer
Conditions
Brief summary
The purpose of the study is to define the safety and tolerability of this drug combination. The study will also define the response rate of patients with advanced and unresectable NSCLC.
Detailed description
This study has a dose escalation (Ib) and dose expansion phase (II). The ALT-803 treatment in the Phase Ib portion of the study will escalate until a recommended dose level is decided. This dose level will be used in the phase II portion of the study. The Phase II potion of the study will include two groups: Nivolumab naive and Nivolumab progressing. Patients will be enrolled to one of the arms based on their previous treatment with Nivolumab.
Interventions
BIOLOGICALALT-803
ALT-803 administered IV at doses per arm (6, 10, 15, 20 µg/kg)
BIOLOGICALNivolumab
Nivolumab administered IV at 3 mg/kg per protocol
Sponsors
Medical University of South Carolina
Altor BioScience
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of NSCLC who present with Stage IIIB/Stage IV disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) or recurrent disease following radiation therapy or surgical resection. 2. Patient must be eligible for treatment with nivolumab. Patients previously treated with nivolumab, pembrolizumab or atezolizumab, and who have progressed are eligible. Patients with targetable with EGFR or ALK mutations are eligible after disease recurrence or progression after at least one targeted therapy for advanced or metastatic disease. 3. Measurable disease as defined by RECIST 1.1 criteria. 4. Age ≥ 18 years 5. Performance status: ECOG performance status of ≤1 (Appendix A) 6. Adequate organ system function within 14 days of registration: ANC ≥ 750/μL (≥0.75 X 109/L) PLT ≥ 100,000/μL (≥ 30 X 109/L) HGB \> 8g/dL Total bilirubin \< 2.0 x ULN AST \< 3.0 X ULN ALT \< 3.0 X ULN eGFR\* \> 45mL/min \*using Cockcroft \& Gault equation (see Appendix B) 7. Negative serum pregnancy test if WOCBP (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized). 8. Female participants of childbearing potential must adhere to using a medically accepted method of birth control up to 28 days prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study. WOCBP must agree to use effective contraception during treatment and for at least 5 months following the last dose of study treatment. 9. Prior to any study specific activities, the patient must be aware of the nature of his/her disease and willingly consent to the study after being informed of study procedures, the experimental therapy, possible alternatives, risks and potential benefits.
Exclusion criteria
1. While prior therapy with nivolumab, pembrolizumab, or atezolizumab is allowed, any prior therapy with other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) is not allowed. 2. NYHA Class III or IV heart failure (Appendix C), uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, or other clinical signs of severe cardiac dysfunction. 3. Symptomatic congestive heart failure, unstable angina pectoris, or myocardial infarction within 6 months of registration. 4. Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds). 5. Patients with CNS metastases with the following exceptions: Patient untreated CNS metastases with 5 or fewer sites of disease, with no single site larger than 20mm, are eligible if they are asymptomatic and not requiring steroids at any dose. Patients with asymptomatic CNS metastases may be treated with radiosurgery before or during therapy on trial without treatment delays. Patients with treated, symptomatic CNS metastases are eligible if they are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to registration AND either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent). 6. Known autoimmune disease requiring active treatment. Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of registration are excluded. Inhaled or topical steroids, and adrenal replacement steroid doses \< 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. 7. Subjects with a history of interstitial lung disease and/or pneumonitis. 8. Known HIV-positive. 9. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy. 10. Positive hepatitis C serology or active hepatitis B infection. Chronic asymptomatic viral hepatitis is allowed. 11. Women who are pregnant or nursing. 12. Psychiatric illness/social situations that would limit compliance with study requirements. 13. Any ongoing toxicity from prior anti-cancer treatment that, in the judgment of the investigator, may interfere with study treatment. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must resolve to grade 1 (NCI CTCAE version 4) or baseline prior to registration. 14. Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days of registration. 15. Other illness that in the opinion of the investigator would exclude the patient from participating in this study, including uncontrolled diabetes mellitus, cardiac disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence or Absence of a Dose Limiting Toxicity (DLT) of ALT-803 in Combination With Nivolumab | Cycles 1-4: Weeks 1-6 of each cycle | A continual reassessment method (CRM) design will be used to identify the maximum tolerated dose (MTD) for Phase Ib patients |
| Objective Response Rate | While on study, at the end of each 6 week cycle; if off study, every 3 months, UP TO 3 YEARS | The phase II portion of the study looks to define the objective response rate (using immune-related RECIST) of ALT-803 added to nivolumab in patients with advanced and unresectable non-small cell lung cancer. Objective response rate will be defined by the best overall response, which is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease, the smallest measurements recorded since the treatment started). The subject's best response assignment will depend on the achievement of both measurement and confirmation criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 6 months | Time from randomization to disease progression or death. |
| Overall Survival (OS) | From first dose until death or last known alive, up to 15 months. | Overall Survival (OS) was defined as the time from first dose of study treatment until death from any cause. Participants without a death event at the time of data cutoff were censored at the date of last known survival status. |
| Duration of Response (DoR) | Up to 6 months | Duration of Response (DoR) was defined as the time from the first documented objective response (CR or PR) until disease progression or death. Participants who had not progressed or died at the time of the data cutoff were censored at the date of last adequate tumor assessment. DoR was evaluated only in participants who achieved an objective response. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn Wrangle, MD
Medical University of South Carolina
Participant flow
Recruitment details
Participants were recruited from \[insert sites or regions\] between \[insert dates\]. The study initially included two exploratory arms; however, no participants were enrolled in these arms. All enrolled participants are represented in the Participant Flow module.
Pre-assignment details
A total of 67 participants completed informed consent and were enrolled per protocol. Of these, 14 participants did not start treatment (withdrawn consent or did not meet eligibility after enrollment). Therefore, 53 participants were assigned to study arms (Arm A: 23; Arm B: 30). No participants were assigned to the exploratory arms.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 10.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 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 | 5 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 28 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 3 / 20 | 3 / 28 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 3 / 20 | 3 / 28 | 0 / 0 | 0 / 0 |
Outcome results
None listed