Ipilimumab, Nivolumab, and Ad.p53-DC in Treating Participants with Relapsed Small Cell Lung Cancer
This phase II trial studies the side effects of ipilimumab, nivolumab, and Ad.p53-DC, and to see how well they work in treating participants with small cell lung cancer that has come back after previous treatment. Monoclonal antibodies, such as ipilimumab and nivolumab, may interfere with the ability of cancer cells to grow and spread. Cancer vaccines, such as Ad.p53-DC, may help the body build an effective immune response to kill cancer cells by telling cells which targets to attack. Giving ipilimumab and nivolumab in combination with Ad.p53-DC, may kill more tumor cells in participants with relapsed small cell lung cancer.
- Histologic or cytologic diagnosis of SCLC
- Recurrence to at least one prior treatment with a platinum containing regimen (cisplatin or carboplatin) including limited stage (LS) and extensive stage (ES) initial presentations * NOTE: In patients with SCLC the most frequent platinum containing doublet used is etoposide-carboplatin; however, etoposide-cisplatin and irinotecan or topotecan combined with either carboplatin or cisplatin are platinum doublet regimens that can sometimes be used and thus would be allowed for the purposes of trial enrollment and eligibility
- Excluded are patients who upon relapse may be still considered for a salvage concurrent chemo-radiation approach
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) >= 1,000 /mcL (within 30 days of treatment initiation)
- Platelets >= 75,000 / mcL (within 30 days of treatment initiation)
- Hemoglobin >= 8 g/dL (within 30 days of treatment initiation)
- Serum creatinine =< 2.0 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) >= 60 mL/min for subject with creatinine levels =< 1.5 X institutional ULN (within 30 days of treatment initiation) * Creatinine clearance (CrCl) should be calculated per institutional standard
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 30 days of treatment initiation)
- Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (within 30 days of treatment initiation)
- Albumin >= 3.0 mg/dL (within 30 days of treatment initiation)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 30 days of treatment initiation)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 30 days of treatment initiation)
- Life expectancy of > 4 months
- Favorable tumor p53 biomarker profile defined by >= 50% p53 positive tumor cells by immunohistochemistry. Tumor p53 biomarker evaluations may be performed with either original or recurrent tumor although samples from recurrent disease are preferred
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment therapy; * NOTE: Systemic steroid doses of =< 10 mg of prednisone daily or its equivalent are allowed in patients receiving physiologic replacement steroid doses
- Has a known history of active TB (Bacillus tuberculosis)
- Hypersensitivity to Ipilimumab and/or nivolumab or any of its excipients
- Has had a prior anti-cancer monoclonal antibody (mAb) excluding any anti-PD-1 and/or anti-PD-L1 checkpoint inhibitor within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer; other malignancies that remain without evidence of disease or recurrence, 2 years or more after curative therapy are also considered part of this exception
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 2 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Any diagnosis of autoimmune disease (confirmed by medical records or appropriate laboratory testing)
- Has known history of, or any evidence of active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days of planned start of study therapy * NOTE: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Locations & Contacts
Contact: Alberto A. Chiappori
Trial Objectives and Outline
I. To determine the disease control rate (DCR) of patients with relapsed (progressive) small cell lung cancer (SCLC) (after standard, first line platinum-doublet chemotherapy) treated with combination immunotherapy (Ad.p53-DC plus ipilimumab-nivolumab).
II. To determine the safety of combination immunotherapy with Ad.p53-DC plus ipilimumab-nivolumab in patients with relapsed (progressive) SCLC.
I. To determine the progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) of combination immunotherapy with Ad.p53-DC plus ipilimumab-nivolumab in patients with relapsed (progressive) SCLC.
II. To determine the immune response (IR) of combination immunotherapy with Ad.p53-DC plus ipilimumab-nivolumab in patients with relapsed (progressive) SCLC.
INDUCTION IMMUNO-THERAPY PHASE: Participants receive ipilimumab intravenously (IV) over 90 minutes and nivolumab IV over 60 minutes on day 1 of courses 1-4. Participants also receive Ad.p53-DC intradermally (ID) or subcutaneously (SC) on days 1 and 15 of course 1, and then again on day 8 of course 2. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE IMMUNO-THERAPY PHASE: Participants receive nivolumab IV over 60 minutes on day 1 beginning on course 5. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Participants also receive Ad.p53-DC SC once every 4 weeks beginning on day 1 of course 5. Courses repeat every 4 weeks for 12 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed-up at 30-45 days and then every 12 weeks for up to 3 years.
Trial Phase & Type
Moffitt Cancer Center
Alberto A. Chiappori
Secondary IDs NCI-2018-00568
Clinicaltrials.gov ID NCT03406715