Summary

for people ages 18 years and up (full criteria)
at UCLA
study started
estimated completion
Edward Garon, M.D. (ucla)

Description

Summary

This is a phase 1 trial of intratumoral administration of CCL21-gene modified dendritic cells combined with intravenous pembrolizumab for advanced non-small cell lung cancer. Up to 12 patients will participate in the dose escalation phase and during dose expansion, 12 patients will be evaluated. Before the first injection of dendritic cells, blood will be collected from the patient and leukapheresis will be performed. Dendritic cells obtained from this blood draw will be cultured and induced with Ad-CCL21 gene. Then, the patient's lung tumor will be injected with these modified dendritic cells. This injection will be followed by treatment with 200 mg intravenous pembrolizumab. Patients will receive an injection of Ad-CCL21 DC followed by treatment with pembrolizumab on Days 0, 21, and 42. After these three injections, patients will receive pembrolizumab 200 mg every three weeks for up to one year. From enrollment of the first patient to the last dose administered to the last subject, this study is anticipated to take approximately 5 years to complete.

Official Title

A Phase I Trial of Intratumoral Administration of CCL21-gene Modified Dendritic Cell (DC) Combined With Intravenous Pembrolizumab for Advanced NSCLC

Details

A phase I, non-randomized, dose escalating, multi-cohort trial followed by dose expansion at the dose established during dose escalation (ExD) will be conducted. During dose escalation, a modified 3+3 design will be used. Three patients will be assigned to each cohort. Patients enrolled into a given cohort will receive the same Ad-CCL21-DC dose by CT-guided or bronchoscopic intratumoral injection followed by intravenous pembrolizumab 200mg one hour after DC injection on days 0, 21, and 42, and intravenous pembrolizumab 200mg every three weeks thereafter for up to a year. The Ad-CCL21-DC dose is 1 x 107 cells/injection in the first cohort (1), and will be increased to 3 x 107 cells/injection (2) pending tolerability in earlier cohort. Dose escalation may proceed only if all 3 patients enrolled in the lower dose cohort experience no DLT or 1 of 6 patients in a cohort has a DLT. If a patient dies within 30 days of receiving investigational treatment and the death is considered to be at least possibly related, further study enrolment will be held until further evaluation by the UCLA DSCMB. If the dose regimen in cohort 1 (Ad-CCL21-DC 1 x 107 cells/injection) is not well tolerated, de-escalation to Ad-CCL21-DC 0.5 x 107 cells/injection will be allowed (-1). If the dose regimen specified for Cohort 2 (Ad-CCL21-DC 3 x 107 cells/injection) is not the maximum tolerated dose (MTD), no further dose escalation will be conducted, and this dose level will be defined as maximum administered dose (MAD).

After completion of the dose-escalation phase, all safety and tolerability data will be reviewed and the ExD will be determined. A dose expansion cohort of 24 patients (D) will be enrolled and treated at ExD for up to a year. All enrolled patients will continue to be followed by a physician, and undergo a history and physical examination every 3 months until progressive disease (PD) or withdrawal from the study. Eligible patients will be assigned to a cohort and will receive intratumoral injections of autologous Ad-CCL21-DC and intravenous pembrolizumab in conjunction with tumor sampling and patient monitoring

Keywords

Carcinoma, Non-Small-Cell Lung Pembrolizumab Ad-CCL21-DC 1 x 07 Ad-CCL21-DC 3 x 07 Ad-CCL21-DC .05 x 07 Ad-CCL21-DC ExD -1 Dose Escalation Dose Expansion

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Adults over the age of 18 capable of giving informed consent.
  2. Stage IV pathologically proven NSCLC.
  3. Staining for PD-L1 in less than half of the tumor cells using the CC23 antibody (0% staining is acceptable)
  4. Measurable disease by RECIST Guidelines (see Appendix B).
  5. ECOG performance status of 0, 1(see Appendix A).
  6. Must be naïve to systemic treatment for NSCLC. Patients who received adjuvant or neo-adjuvant chemotherapy
  7. Adequate renal function (defined as BUN≤40 or serum creatinine≤2).
  8. Adequate liver function (defined as serum total bilirubin≤2X the upper limits of normal (ULN), or serum transaminases≤3X ULN).
  9. Adequate coagulation parameters (defined as PT and/or PTT≤1.5X ULN or platelets≥100,000).
  10. . Adequate neutrophils (defined as absolute neutrophil count≥1,500/mm3).
  11. . In woman who have not experienced menopause, negative pregnancy test prior to initiation of treatment and adequate contraception throughout treatment.
  12. . All subjects must demonstrate adequate respiratory function (defined as SaO2 >90% on room air; PCO2 <45mmHg; or FEV1 >1.0 liter).
  13. . Patients with a major endobronchial lesion in the segmental, lobar, or mainstem bronchus with complete obstruction of the airway may be eligible for bronchoscopic injection if there is no evidence of respiratory failure (defined as SaO2 >90% on room air; PCO2 <45mmHg; or FEV1 >1.0 liter).
  14. . Patients with an endobronchial lesion in the segmental bronchus with variable stenosis (not completely obstructed) and not amenable to standard palliative airway treatments (i.e. laser and stenting) may be eligible for bronchoscopic injection if there is no evidence of respiratory failure (defined as SaO2 >90% on room air; PCO2 <45mmHg; or FEV1 >1.0 liter).
  15. . Subjects with bullous disease may undergo CT-guided transthoracic injection if the targeted tumor has an intended needle path without crossing bullae.

You CAN'T join if...

  1. Previous systemic therapy for Stage IV NSCLC, including chemotherapy, radiation therapy or non-cytotoxic investigational agents.
  2. Comorbid disease or a medical condition that would impair the ability of the patient to receive or comply with the study protocol.
  3. Any use of systemic corticosteriods within 10 days of treatment or during treatment.
  4. Renal insufficiency (defined as BUN>40 or serum creatinine>2).
  5. Liver insufficiency (defined as serum total bilirubin > 2x ULN, or serum transaminases > 3X ULN). Note: Transaminases can be up to 5X ULN in the setting of liver metastases
  6. Coagulopathy (defined as PT and/or PTT > 1.5X ULN or platelets < 100,000).
  7. Neutropenia (defined as absolute neutrophil count < 1,500/mm3).
  8. Respiratory failure (defined as SaO2 <90% on room air; PCO2 >44mmHg; or FEV1 <1.0 liter)
  9. Acute viral, bacterial, or fungal infection, which requires specific therapy. Acute therapy must have been completed within 14 days prior to study treatment.
  10. . HIV infected patients.
  11. . Hypersensitivity to any reagents used in the study.
  12. . Pregnancy or inadequate contraception.
  13. . Lactating females.
  14. . Active CNS metastasis, which has not been treated with radiation therapy
  15. . Subjects with organ allografts.
  16. . Subjects with bullous disease may not undergo CT-guided transthoracic injection if the targeted tumor has an intended needle path that requires crossing the bullae.
  17. . Previous or concurrent evidence of autoimmune disease requiring systemic steroids.
  18. . Patients with a major endobronchial lesion in the lobar or mainstem bronchus amenable to standard palliative airway treatments or with >50% stenosis (not completely obstructed airway) will be excluded from bronchoscopic injection.

Sample

Location

  • University of California at Los Angeles accepting new patients
    Los Angeles California 90095 United States

Lead Scientist

  • Edward Garon, M.D. (ucla)
    Health Sciences Associate Clinical Professor, Medicine. Authored (or co-authored) 104 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Jonsson Comprehensive Cancer Center
ID
NCT03546361
Phase
Phase 1
Study Type
Interventional
Last Updated