E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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) |
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E.1.1.1 | Medical condition in easily understood language |
Part 1: advanced or metastatic solid tumors
Part 2: advanced or metastatic endometrium cancer, ovarian cancer, renal cell carcinoma (RCC), melanoma, and non–small cell lung cancer (NSCLC) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014734 |
E.1.2 | Term | Endometrial cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038407 |
E.1.2 | Term | Renal cell cancer |
E.1.2 | System Organ Class | 100000072939 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057529 |
E.1.2 | Term | Ovarian cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027150 |
E.1.2 | Term | Melanoma malignant |
E.1.2 | System Organ Class | 100000018529 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• 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.
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E.2.2 | Secondary objectives of the trial |
• To evaluate the pharmacokinetics (PK) of INCAGN01949 in subjects with advanced or metastatic solid tumors.
• 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).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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 carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the subject has been disease-free for > 1 year, after treatment with curative intent.
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
• History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
• Active infection requiring systemic therapy.
• Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation.
• Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
• Known allergy or reaction to any component of study drug or formulation components.
• Prior treatment with an OX40 agonist for any indication.
• Is a female who is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 60 days after the last dose of study drug.
• Is a male who is expected to father children within the duration of the study, starting with the screening visit through 90 days after the last dose of study drug.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety and tolerability will be assessed by monitoring the frequency, duration, and severity of adverse events (AEs). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The PK of INCAGN01949, including Cmax, Tmax, Cmin, and AUC0-t for subjects in Parts 1 and 2 will be summarized.
• Objective response rate, defined as the percentage of subjects having complete response (CR) or partial response (PR), will be determined by investigator assessment of radiographic disease per RECIST v1.1 and mRECIST v1.1.
• Duration of response, defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, will be determined by investigator assessment of radiographic disease per RECIST v1.1 and mRECIST v1.1, or death from any cause, if occurring sooner than progression.
• Progression-free survival, defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease per RECIST v1.1 and mRECIST v1.1, or death from any cause if occurring sooner than progression.
• Duration of disease control (CR, PR, and stable disease [SD]) as measured from first report of SD or better until disease progression, will be determined by investigator assessment of radiographic disease per RECIST v1.1 and mRECIST v1.1, or death from any cause, if occurring sooner than progression. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Spain |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 1 |