Study of efficacy and safety of NIR178 and PDR001 combination in patients with selected solid tumors and non-Hodgkin lymphoma
- Conditions
- MedDRA version: 20.0Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]Advanced solid tumors and non-Hodgkin lymphomaMedDRA version: 20.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2017-000241-49-IT
- Lead Sponsor
- OVARTIS PHARMA AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
- Histologically documented advanced or metastatic solid tumors or lymphomas
. Part 1: histologically confirmed renal cell carcinoma (RCC), pancreatic cancer, urothelial cancer, head and neck cancer, diffuse large B-cell lymphoma (DLBCL), microsatellite stable (MSS) colon cancer, triple negative breast cancer (TNBC) or melanoma
. Part 2: histologically confirmed diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant
histology
. Part 3: histologically confirmed diagnosis of advanced/metastatic NSCLC and one additional tumor type based on emerging data from part
1 of the study.
- Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and again during therapy on this study. The collection of recent sample is permitted under the following conditions (both must be met):
. Biopsy was collected = 3 months before 1st dose of study treatment and available at the site.
. No immunotherapy was given to the patient since collection of biopsy.
- Patients must previously have received at least 1 and no more than 3 prior lines of therapy for their disease
- Patients must not have received prior immunotherapy (previous immune checkpoint inhibitors; single agent and/or combination therapy
with anti-CTLA-4, anti-PD-1, anti-PD-L1), except for NSCLC patients enrolled in part 3
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest
diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or as >10 mm with
spiral computer tomography (CT) scan, Magnetic Resonance Imaging (MRI), or calipers by clinical exam.
Other protocol defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180
- Ongoing or prior treatment with A2aR inhibitors. Patients previously treated with A2aR inhibitors for non-oncologic indications (e.g. Parkinson's disease) may be considered for enrollment on a case by case basis.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of PDR001, with the exception of intranasal/inhaled
corticosteroids or systemic corticosteroids at physiological doses (not exceeding equivalent of 10 mg/day of prednisone)
- History of interstitial lung disease or non-infectious pneumonitis
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease =2 years before the first dose of study drug and of low potential
risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Active or prior documented autoimmune disease within the past 2 years. Patients with vitiligo, Grave's disease, or psoriasis not requiring
systemic treatment (within the past 2 years) are not excluded.
- More than 3 prior lines of therapy
- Participation in another clinical study with an investigational product during the last 21 days prior to starting on treatment.
Other protocol defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: - Part 1:To evaluate the efficacy of NIR178 and PDR001 combination in patients with selected advanced solid tumors and diffuse large B cell<br>lymphoma (DLBCL)<br>- Part 2: To assess the efficacy of several intermittent dosing schedules of NIR178 in combination with PDR001 in NSCLC<br>- Part 3: To evaluate efficacy of intermittent dosing schedule of NIR178 in NSCLC and another tumor type;Secondary Objective: - To assess efficacy of NIR178+PDR001 in select advanced solid tumors and lymphoma<br>- To assess the safety and tolerability of the NIR178 and PDR001 combination<br>- To characterize changes in the immune infiltrate in tumors<br>- To characterize the pharmacokinetics (PK) of NIR178, its metabolite NJI765 and PDR001 in combination<br>- To assess immunogenicity of PDR001;Primary end point(s): ORR;Timepoint(s) of evaluation of this end point: At protocol define timepoints until End of study.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - DCR, DoR, PFS, 2 years Overall Survival rate<br>- Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters. Dose interruptions, reductions and dose intensity.<br>- Change from baseline in TILs<br>- Plasma concentration time profiles of NIR178, NJI765 and PK parameters. Serum concentration time profiles of PDR001 and PK parameters.<br>- Presence and/or concentration of anti-PDR001 antibodies;Timepoint(s) of evaluation of this end point: At protocol define timepoints until End of study.