A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors

Phase 1

• Conditions: Part 1: advanced or metastatic solid tumors Part 2: advanced or metastatic adenocarcinoma of the endometrium, ovarian cancer, renal cell carcinoma (RCC), melanoma, and non–small cell lung cancer (NSCLC); MedDRA version: 20.0 Level: PT Classification code 10014734 Term: Endometrial cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10038407 Term: Renal cell cancer System Organ Class: 100000072939; MedDRA version: 20.0 Level: PT Classification code 10057529 Term: Ovarian cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10027150 Term: Melanoma malignant System Organ Class: 100000018529; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002079-93-GB
• Lead Sponsor: Incyte Biosciences International Sàrl

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-03-23
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 163

Inclusion Criteria

• Men and women, aged 18 or older.
• Willingness to provide written informed consent for the study.
• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
• Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
• Part 1: Subjects with advanced or metastatic solid tumors.
• Part 2: Subjects with advanced or metastatic adenocarcinoma of the endometrium, ovarian cancer, RCC, melanoma, and NSCLC.
-For subjects with adenocarcinoma of the endometrium: should have documented microsatellite instability (MSI) status (eg, MSI-high, MSI-low, microsatellite stable), or consent to MSI status testing during the screening period.
-For subjects with ovarian cancer: histologically confirmed diagnosis of ovarian, fallopian, or primary peritoneal carcinoma of epithelial origin.
-For subjects with NSCLC (squamous and nonsquamous): should have documentation of driver mutation testing for anaplastic lymphoma kinase, epidermal growth factor receptor status, BRAF mutation status, or consent to testing for these markers during the screening period.
-For subjects with RCC: must have histologically confirmed diagnosis of RCC that is predominantly clear cell histology.
-For subjects with melanoma: mucosal or cutaneous melanoma is acceptable; however, subjects with ocular melanoma are excluded. Subjects should have documented BRAF mutation status or consent to BRAF mutation testing during the screening period.
• Presence of measureable disease based on RECIST v1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other locoregional therapy, are not considered measureable unless there has been demonstrated progression in the lesion.
• Part 1 Safety Expansion and Part 2: Willingness to undergo pretreatment and on-treatment tumor biopsies (core or excisional).
• ECOG performance status 0 or 1.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 81
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 82

Exclusion Criteria

• Laboratory and medical history parameters not within the Protocol-defined range. If the screening laboratory tests below were conducted > 7 days before treatment initiation, they will need to be repeated on Day 1 before initiation of treatment.
-Absolute neutrophil count < 1.5 × 109/L.
-Platelets < 100 × 109/L.
-Hemoglobin < 9 g/dL or < 5.6 mmol/L.
-Serum creatinine > 1.5 × institutional upper limit of normal (ULN), OR measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) < 50 mL/min for subjects with creatinine levels > 1.5 × ULN.
-Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase = 2.5 × ULN.
-Total bilirubin = 1.2 × ULN unless conjugated bilirubin = ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then direct bilirubin must be < 40% of total bilirubin.
-International normalized ratio, prothrombin time, or activated partial thromboplastin time > 1.5 × ULN.
• Transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony–stimulating factor, granulocyte macrophage colony–stimulating factor, or recombinant erythropoietin) within 14 days before study Day 1.
• Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study drug:
-= 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Subjects must also not require chronic use of corticosteroids and must not have had radiation pneumonitis as a result of treatment. A 1-week washout is permitted for palliative radiation to non–central nervous system (CNS) disease with sponsor approval.
-= 28 days for prior immunotherapy or persistence of active cellular therapy (ie, chimeric antigen receptor T-cell therapy; other cellular therapies must be discussed with medical monitor to determine eligibility).
-= 28 days for a prior monoclonal antibody used for anticancer therapy with the exception of denosumab.
-= 7 days for immune-suppressive–based treatment for any reason.
-= 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational agents or devices. For investigational agents with long half-lives (eg, > 5 days), enrollment before the fifth half-life requires medical monitor approval.
• Has not recovered to = Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting therapy.
• Receipt of a live vaccine within 30 days of planned start of study drug.
• Active autoimmune disease that required systemic treatment in the past (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Known active CNS metastases and/or carcinomatous meningitis.
• Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcin

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Throughout the study;<br> Main Objective: • To evaluate the safety, tolerability, and dose-limiting toxicities (DLTs) of INCAGN01949 and to define a maximum tolerated dose (MTD) or pharmacologically active dose (PAD) of INCAGN01949 in subjects with metastatic or advanced solid tumors.<br> ;Primary end point(s): • Safety and tolerability will be assessed by monitoring the frequency, duration, and severity of adverse events (AEs).;<br> Secondary Objective: • To evaluate the pharmacokinetics (PK) of INCAGN01949 in subjects with advanced or metastatic solid tumors.<br> • To evaluate the preliminary efficacy of INCAGN01949 by assessing the objective response rate, duration of response, progression-free survival, and duration of disease control per RECIST v1.1 and modified RECIST v1.1 (mRECIST v1.1).<br>