A Phase 1/1b First-In-Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 Monotherapy and in Combination With Nivolumab in Subjects With Advanced Solid Tumors

Infinity Pharmaceuticals, Inc.11 sites in 1 country219 target enrollmentDecember 2015

ConditionsAdvanced Solid Tumors (Part A/B/C/D)Non-small Cell Lung Cancer (Part E)Melanoma (Part E)Squamous Cell Cancer of the Head and Neck (Part E)Triple Negative Breast Cancer (Part F)Adrenocortical Carcinoma (Part G)Mesothelioma (Part G)High-circulating Myeloid-derived Suppressor Cells (Part H)

InterventionsIPI-549 (eganelisib)Nivolumab

DrugsIPI-549 (eganelisib)Nivolumab

Overview

Phase: Phase 1
Intervention: IPI-549 (eganelisib)
Conditions: Advanced Solid Tumors (Part A/B/C/D)
Sponsor: Infinity Pharmaceuticals, Inc.
Enrollment: 219
Locations: 11
Primary Endpoint: Part D/E: Adverse Events (AE) and safety laboratory values
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IPI-549 monotherapy and IPI-549 in combination with nivolumab in subjects with advanced solid tumors.

Detailed Description

Study IPI-549-01 is a first-in-human multicenter, open-label, up to five-part Phase 1/1b dose-escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of IPI-549 monotherapy and IPI-549 in combination with nivolumab in subjects with advanced solid tumors. Approximately 175 subjects will receive IPI-549, either as a monotherapy or in combination with nivolumab. Subjects will receive IPI-549 until the maximum tolerated dose (MTD) is achieved or until disease progression or unacceptable toxicity. Part A (QD dosing) (and Part B (BID dosing) if necessary) a dose escalation part of the study will evaluate the safety and tolerability, PK, and PD of IPI-549 as a single agent in subjects with advanced solid tumors. Part A/B will determine the recommended phase 2 dose (RP2D) for IPI-549 single agent that is going to be administered in Part D as a single agent and Part C in combination with nivolumab. Part C a dose-escalation part of the study will evaluate the safety and tolerability, PK, and PD of IPI-549 when administered in combination with IV nivolumab 240 mg every 2 weeks (Q2W) in subjects with advanced solid tumors. Part C will determine the RP2D for the combination of IPI-549 and nivolumab (combination RP2D). Part D will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 administered as a single agent in a cohort of subjects with advanced solid tumors. Part D, Cycle 2 will also include a pilot food (a high-fat meal) effect evaluation that will have 8 subjects out of the entire cohort of subjects participating in the Part D. Part E will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with non-small cell lung cancer (NSCLC), a cohort of subjects with melanoma and a cohort of subjects with Squamous Cell Cancer of the Head and Neck (SCCHN). One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. To be eligible for enrollment in Part E, subjects must have received an anti-PD1/PD-L1 as their most recent treatment prior to study entry. The dose level to be administered in Part E will be the combination RP2D as determined in Part C. Part F will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with triple negative breast cancer (TNBC). One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. To be eligible for enrollment in Part E, subjects must have no prior anti-PD1/PD-L1 therapy. The dose level to be administered in Part E will be the combination RP2D as determined in Part C. Part G will evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of IPI-549 in combination with intravenous (IV) nivolumab 240 mg Q2W in a cohort of subjects with adrenocortical carcinoma (ACC) and a cohort of subjects with mesothelioma who have received at least first line available therapy. One or more cohorts of subjects with additional tumor types may be enrolled if supported by data generated in dose escalation or earlier expansion cohorts. The dose level to be administered in Part E will be the combination RP2D as determined in Part C. Part H will evaluate the safety, tolerability, PK, and preliminary clinical activity of IPI-549 in combination with IV nivolumab 240 mg Q2W in subjects with advanced cancer with high-circulating MDSCs (ie, ≥ 20.5% as measured by Serametrix CLIA-certified assay); other indication(s) are to be determined. For subject's with a microsatellite instability-high tumor, or tumor type for which anti-PD-1/anti-PD-L1 therapy is considered standard of care, that subject must have previously received an anti-PD-1 or anti-PD-L1 therapy.

Registry

clinicaltrials.gov

Start Date

December 2015

End Date

December 2022

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Infinity Pharmaceuticals, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•All subjects must meet the following criteria for inclusion:
•≥ 18 years of age
•Life expectancy of ≥ 3 months
•Histological or cytological evidence of advanced and/or metastatic carcinoma or melanoma , excluding sarcoma
•At least 1 measurable disease lesion as defined by RECIST 1.1
•Serum creatinine clearance ≥ 60 mL/min and serum creatinine ≤ 2.0 x the upper limit of normal (ULN) as determined by either of the following: Estimation as calculated by Cockcroft-Gault equation or Direct measurement by 24-hour urine collection
•Total bilirubin ≤ 1.5 x ULN (unless elevated due to Gilbert's syndrome)
•Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 x ULN (\<5x ULN if liver metastasis)
•Adequate hematological function, defined as absolute neutrophil count ≥1.5 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L
•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (corresponds to Karnofsky Performance Status (KPS) ≥ 60%)

Exclusion Criteria

•Subjects are to be excluded from the study if they meet any of the following criteria:
•Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any excipient in the study drugs
•Major surgery within 4 weeks prior to Screening
•Subjects who have been treated with chemotherapy, biologic therapy, or other investigational agent within \< 5 times the half-life of the agent or \< 28 days (whichever is shorter) of starting study drug
•NOTE: Subjects whose immediate prior treatment was with nivolumab may start study drug 2 weeks after the last dose of nivolumab
•Symptomatic or untreated brain metastases
•Primary central nervous system (CNS) malignancy
•Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus
•Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids
•Ongoing systemic bacterial, fungal, or viral infections at Screening

Arms & Interventions

Part A/B: IPI-549 Dose Escalation

Participants receive IPI-549 orally (PO) once a day (QD) for Part A and twice a day (BID) in Part B until disease progression.