Advanced Cancer, Advanced Solid Tumor, ALK Genomic Tumor Aberrations, Anaplastic Lymphoma Kinase Genomic Tumor Aberrations, Colorectal Cancer, Hepatocellular Cancer, Hepatocellular Carcinoma, Kidney Cancer, Melanoma, Metastasis, Mismatch Repair Deficiency, MSI-High, Non Small Cell Lung Cancer, NSCLC, Pleural Mesothelioma, Renal Cell Cancer, Renal Cell Carcinoma, Skin Cancer
Conditions
Keywords
Phase 1, Phase 1b, 7 Hills Pharma
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.
Interventions
DRUGAlintegimod
Alintegimod will be provided in bottles of 30 softgel capsules for oral administration
DRUGIpilimumab
Ipilimumab (Yervoy) will be administered via IV
DRUGNivolumab
Nivolumab (Opdivo) will be administered via IV
Sponsors
7 Hills Pharma, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Phase 1b - Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion and
Exclusion criteria
for Phase 1b Inclusion Criteria 1. Adult patients (age 18 or older) 2. 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-L1. 3. 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. 4. ECOG performance status of 0 or 1. 5. Has a life expectancy of \> 12 weeks. 6. 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. 7. Men receiving the investigational drug and are sexually active with women of child-bearing potential (WCBP) must use contraception during treatment and for 5 half-lives after the last dose of the investigational drug or Women, not otherwise meeting other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants treated with Alintegimod monotherapy with treatment related adverse events as assessed by CTCAEv5.0 | 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 | 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 |
| Define RPTDs for Alintegimod | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize Pharmacokinetics of Alintegimod monotherapy by measuring Maximum Plasma Concentration (Cmax) | 1 year | To characterize the pharmacokinetics of Cmax of Alintegimod monotherapy. |
| Characterize Pharmacokinetics of Alintegimod monotherapy by measuring Area Under the Curve (AUC) | 1 year | To characterize the pharmacokinetics of AUC of Alintegimod monotherapy. |
| Characterize Pharmacokinetics of Alintegimod plus ipilimumab by measuring Maximum Plasma Concentration (Cmax) | 1 year | To characterize the pharmacokinetics of Cmax of Alintegimod in combination with ipilimumab. |
| Characterize Pharmacokinetics of Alintegimod plus ipilimumab by measuring Area Under the Curve (AUC) | 1 year | To characterize the pharmacokinetics of AUC of Alintegimod in combination with ipilimumab. |
| 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 | To assess the progression-free survival of patients treated with Alintegimod in combination with ipilimumab followed by nivolumab monotherapy, using RECIST v1.1 assessment for progression. |
| Determine Overall Response Rate (ORR) in patients treated with Alintegimod plus ipilimumab followed by nivolumab using RECIST v1.1 response assessment criteria. | 18 months | To assess the overall response rate of patients treated with Alintegimod in combination with ipilimumab followed by nivolumab monotherapy, using RECIST v1.1 assessment for progression. |
Countries
United States
Contacts
CONTACTSr. Director Clinical Affairs
CONTACTVP Clinical Affairs and Regulatory
STUDY_CHAIRLionel Lewis, MA, MB.Bch, MD
7 Hills Pharma
Outcome results
None listed