A Phase 1b/2a Multi-Center, Dose Escalation and Reference Regimen-Controlled, Multi-Cohort Study to Determine the Safety and Efficacy of Oral 7HP349 (Alintegimod) in Combination With Ipilimumab Followed by Nivolumab Monotherapy in Patients With Locally Advanced or Metastatic Cancers Following One or More Prior Therapies
Overview
- Phase
- Phase 1
- Intervention
- Ipilimumab
- Conditions
- Advanced Cancer
- Sponsor
- 7 Hills Pharma, LLC
- Enrollment
- 126
- Locations
- 9
- Primary Endpoint
- Define RPTDs for Alintegimod
- Status
- Recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
This study is an open-label Phase Ib (Part A) dose escalation followed by a blinded, randomized, multi cohort Phase 2a (Part B) comparison of combination vs. reference regimens.
Currently study will only be enrolling the Phase 1b and the Phase 2a protocol requirements will be added to the study near completion of the Phase 1b
Detailed Description
This Phase study is designed to evaluate the safety, tolerability, and preliminary efficacy of oral Alintegimod (Alintegimod) alone, and then in combination with ipilimumab for, followed by nivolumab monotherapy cycles. All patients will receive nivolumab after completion of treatment with Alintegimod plus ipilimumab combination therapy to continue nivolumab treatment until the end of study (12 months) unless progression or toxicity result in early termination.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Inclusion and
Exclusion Criteria
- •for Phase 1b
- •Inclusion Criteria
- •Adult patients (age 18 or older)
- •Patient has a histologically confirmed diagnosis of any of the following locally advanced or metastatic solid tumors: melanoma, pleural mesothelioma, renal cell carcinoma, MSI-high or mismatch repair-deficient colorectal cancer, hepatocellular carcinoma, and non-small cell lung cancer with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, or tumor types for which the combination of ipilimumab and nivolumab has been FDA approved. Patients may have received treatment with anti PD-1/PD-L
- •ANC ≥ 1000/µL without use of G-CSF, Hgb ≥ 9 g/dL without required blood transfusion for at least 5 days prior to pretreatment baseline, and platelet count ≥ 75,000/µL without transfusions for at least 5 days prior to pretreatment baseline.
- •ECOG performance status of 0 or
- •Has a life expectancy of \> 12 weeks.
- •Renal and hepatic function requirements:
- •a. Renal function with either an eCrCL ≥ 60 mL/min (modified Cockcroft-Gault) or eGFR ≥ 60 mL/min/1.73 m2 (using MDRD or CKD-EPI or similar equations).
- •b. Hepatic function with ALT/AST ≤ 3 x ULN, total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert Syndrome). If patients have hepatic metastases, then AST/ALT≤ 5 x ULN will be allowed.
Arms & Interventions
Dose Escalation - Open Label Phase 1b
Alintegimod dose escalation, 4 cohorts Alintegimod monotherapy 1 cycle Alintegimod + Ipilimumab - 4 cycles Nivolumab - 11 cycles
Intervention: Ipilimumab
Dose Escalation - Open Label Phase 1b
Alintegimod dose escalation, 4 cohorts Alintegimod monotherapy 1 cycle Alintegimod + Ipilimumab - 4 cycles Nivolumab - 11 cycles
Intervention: Nivolumab
Dose Escalation - Open Label Phase 1b
Alintegimod dose escalation, 4 cohorts Alintegimod monotherapy 1 cycle Alintegimod + Ipilimumab - 4 cycles Nivolumab - 11 cycles
Intervention: Alintegimod
Outcomes
Primary Outcomes
Define RPTDs for Alintegimod
Time Frame: 18 months
To define two doses of the Alintegimod + ipilimumab followed by nivolumab cohorts that will be used in the Phase 2a (Part B) study.
Number of participants treated with Alintegimod monotherapy with treatment related adverse events as assessed by CTCAEv5.0
Time Frame: 1 year
To evaluate the safety and tolerability of Alintegimod administered as monotherapy, in the patients with adverse events as assessed by CTCAE v5.0 and coded by System Organ Class (SOC) using MedDRA coding dictionary
Number of participants treated with Alintegimod in combination with treatment related adverse events as assessed by CTCAEv5.0
Time Frame: 1 year
To evaluate the safety and tolerability of Alintegimod administered in combination with ipilimumab followed by sequential nivolumab monotherapy, in the number of patients with adverse events as assessed by CTCAE v5.0 and coded by System Organ Class (SOC) using MedDRA coding dictionary
Secondary Outcomes
- Characterize Pharmacokinetics of Alintegimod monotherapy by measuring Maximum Plasma Concentration (Cmax)(1 year)
- Characterize Pharmacokinetics of Alintegimod monotherapy by measuring Area Under the Curve (AUC)(1 year)
- Characterize Pharmacokinetics of Alintegimod plus ipilimumab by measuring Maximum Plasma Concentration (Cmax)(1 year)
- Characterize Pharmacokinetics of Alintegimod plus ipilimumab by measuring Area Under the Curve (AUC)(1 year)
- Determine Progression Free Survival (PFS) response in patients treated with Alintegimod plus ipilimumab followed by nivolumab using RECIST v1.1 tumor assessment criteria.(18 months)
- Determine Overall Response Rate (ORR) in patients treated with Alintegimod plus ipilimumab followed by nivolumab using RECIST v1.1 response assessment criteria.(18 months)