A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549

Status unconfirmed · Phase 1

Conditions studied: Advanced 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)

In brief

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.

Key facts

Study ID: NCT02637531
Run by: Infinity Pharmaceuticals, Inc.
People needed: 219
Starts: 2015-12-01
Expected to finish: 2022-12-01
Last updated by the study team: 2022-04-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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%)
Subjects entering Part A, B, C, or D must also meet the following additional criterion:
Failure to respond to standard therapy, or for whom no appropriate therapies are available (based on the judgement of the Investigator)
Subjects entering Part D, E, F or G must also meet the following additional criterion:
Willing to undergo 1 pre-treatment and 1 on-treatment tumor biopsy
Subjects entering Part E must also meet the following additional criteria:
Histological or cytological evidence of NSCLC, melanoma, , human papillomavirus (HPV) positive or HPV negative SCCHN (oral cavity, pharynx, hypopharynx, larynx, nasopharyngeal [including undifferentiated nasopharyngeal carcinoma]), or another tumor type to be determined
Failure to respond to standard therapy, or for whom no appropriate therapies are available (based on the judgment of the Investigator The most recent treatment prior to study entry must be an anti-PD-1 or anti-PD-L1 antibody given as either monotherapy or in combination
Subjects with NSCLC Tumors that harbor an actionable genetic alteration for which there is a corresponding approved therapy for that specific alteration (including but not limited to alterations in EGFR, ALK, and ROS) must have progressed on, or had intolerance to, the respective therapy
Subjects entering Part F must also meet the following additional criteria:
Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing, based on last available tumor tissue; or another tumor type to be determined
ER/PgR negativity to follow local guidelines
If IHC HER2 2+, a negative FISH test is required
Inflammatory triple negative breast cancer is allowed
Must have received and failed/progressed a cytotoxic chemotherapy as first line therapy per standard of care
No prior anti-PD-1 or anti-PD-L1 therapy

You may not qualify if…

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
NOTE: Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met
Administration of a live vaccine within 6 weeks of first dose of study drug
Administration of any of the following within 1 week prior to the administration of study drug:
Strong inhibitors or inducers of CYP3A4, including grapefruit products and herbal supplements
P-glycoprotein (P-gp) inhibitors
Warfarin, phenytoin, or other substrates of CYP2C8 or CYP2C9 with a narrow therapeutic range
Medications associated with QTc interval prolongation or Torsades de Pointes
Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of triplicate readings) NOTE: criterion does not apply to subjects with a right or left bundle branch block
Parts C, D-Annex, and E only: Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia
Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
History of peptic ulcer and/or gastrointestinal bleed
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening
Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the subject associated with his or her participation in the study.

Where it is running

UCSD — San Diego, California, United States
UCLA — Santa Monica, California, United States
Hematology Oncology Associates of the Treasure Coast — Port Saint Lucie, Florida, United States
Emory University — Atlanta, Georgia, United States
Massachusetts General Hospital — Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
Hackensack University Medical Center — Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center — New York, New York, United States
MD Anderson Cancer Center — Houston, Texas, United States
South Texas Accelerated Research and Treatment (START) — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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