Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

This phase I/II trial is designed to efficiently identify the regimen limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the combination of the immunotherapeutic agent indoximod when administered in combination with standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. All subjects will receive the same standard gemcitabine plus nab-paclitaxel regimen, plus indoximod in doses increasing from 600 mg twice daily to, potentially, 1200 mg twice daily.

Detailed description public domain (ClinicalTrials.gov)

This is a Phase I/II trial designed to evaluate the combination of the immunotherapeutic agent indoximod and the standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. The phase 1 portion is designed to identify the regimen-limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the combination. The phase 2 portion of the study will evaluate the potential efficacy of this combination. All subjects will receive the standard 28-day gemcitabine plus nab-paclitaxel regimen. Twice daily oral indoximod will be administered concurrently in continuous 28 day cycles. In the phase 1 portion, dose escalation of indoximod will begin at 600 mg twice a day and potentially escalate to 1200 mg twice a day. There will be no intra-subject dose escalation. Regimen-limiting toxicity will be considered as those toxicities related to indoximod that significantly limit the administration of the backbone chemotherapy gemcitabine plus nab-paclitaxel. The period for determination of dose-limiting toxicities will be the initial 28 days of treatment. The recommended phase 2 dose will include an assessment of toxicities that occur at later time points. Once a RP2D is determined, the phase 2 portion of the study will be initiated. In both phase 1 and phase 2, every 2 cycles subjects will have repeat imaging to assess response. Corollary biomarkers will be assessed at the same interval as will PET-CT after the 1st 8 week cycle. Up to 18 patients will be enrolled in the phase 1 portion of the study and 80 patients will be enrolled in the phase 2 portion.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Regimen Limiting Toxicity [10 months]. Count Of Participants, Participants. Phase 1 Dose Level 1 (n=6): 0; Phase 1 Dose Level 2 (n=3): 0; Phase 1 Dose Level 3 (n=6): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival [22 months]. Median, Weeks (95% Confidence Interval). Phase 2 Efficacy Evaluable and Biopsy Cohort (n=103): 47.9 (40.3 to 59.3); Phase 2 Intent to Treat Cohort (n=135): 39.1 (31.9 to 47.3).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Response Rate [22 months]. Count Of Participants, Participants. Complete Response: Phase 2 Efficacy Evaluable and Biopsy Cohort (n=103): 2; Phase 2 Intent to Treat Cohort (n=135): 2. Partial Response: Phase 2 Efficacy Evaluable and Biopsy Cohort (n=103): 46; Phase 2 Intent to Treat Cohort (n=135): 46. No Response: Phase 2 Efficacy Evaluable and Biopsy Cohort (n=103): 55; Phase 2 Intent to Treat Cohort (n=135): 87.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival [22 months]. Median, Weeks (95% Confidence Interval). Phase 2 Efficacy Evaluable and Biopsy Cohort (n=103): 32.1 (25.1 to 35); Phase 2 Intent to Treat Cohort (n=128): 26.6 (22.1 to 32.3).