E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid tumors and non-Hodgkin lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Advanced solid tumors and non-Hodgkin lymphoma |
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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 | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
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 | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
- Part 1:To evaluate the efficacy of NIR178 and PDR001 combination in patients with selected advanced solid tumors and diffuse large B cell lymphoma (DLBCL)
- Part 2: To assess the efficacy of several intermittent dosing schedules of NIR178 in combination with PDR001 in NSCLC
- Part 3: To evaluate efficacy of intermittent dosing schedule of NIR178 in NSCLC and another tumor type
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E.2.2 | Secondary objectives of the trial |
- To assess efficacy of NIR178+PDR001 in select advanced solid tumors and lymphoma
- To assess the safety and tolerability of the NIR178 and PDR001 combination
- To characterize changes in the immune infiltrate in tumors
- To characterize the pharmacokinetics (PK) of NIR178, its metabolite NJI765 and PDR001 in combination
- To assess immunogenicity of PDR001
- Japanese Safety Run-in (To assess the preliminary safety, and PK of
single agent NIR178 in Japanese patients) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologically documented advanced or metastatic solid tumors or lymphomas
a.Part 1: renal cell carcinoma (RCC), pancreatic cancer, urothelial cancer, head and neck squamous cell carcinoma (HNSCC), diffuse large
B-cell lymphoma (DLBCL), microsatellite stable colorectal cancer (MSS CRC), triple negative breast cancer (TNBC) or cutanous melanoma
- Patients with CRC must have MSS disease as detected by PCR-based assay or mismatch repair proficient loss of MMR protein expression as
detected by immunohistochemistry and confirmed RAS genotype by standard testing of tumor specimen based on local laboratory data
- Patients with unresectable or metastatic cutaneous melanoma that have confirmed BRAF V600E status by standard testing of tumor specimen by local laboratory data
b.Part 2: histologically confirmed diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant
histology
- Patients should have confirmed EGFR and ALK genotype when clinically indicated and performed per standard testing of tumor specimen based on local laboratory data
c.Part 3: histologically confirmed diagnosis of advanced/metastatic NSCLC and one additional tumor type based on emerging data from part
1 of the study.
2.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:
. Biopsy was collected ≤ 6 months before 1st dose of study treatment and available at the site
. No immunotherapy since collection of biopsy
3.Patients (other than those with DLBCL) must previously have received at least 1 and no more than 3 prior lines of therapy for their disease:
• MSS Colorectal Cancer (MSS CRC):
- Patients with MSS CRC must have received (or be intolerant to) prior therapy with fluoropyrimidine-oxaliplatin- and irinotecan- based
regimens
- Patient with wt RAS must have received prior treatment with an antibody targeting EGFR (e.g. cetuximab or panitumumab)
• Triple Negative Breast Cancer (TNBC):
- Patients with TNBC must have received a prior taxane- containing regimen
• Urothelial Cancer:
- Patients with urothelial cancer must have received a prior platinumcontaining regimen or be ineligible for cisplatin
• Renal Cell Carcinoma (RCC):
- Patients with RCC must have received a prior VEGF tyrosine kinase inhibitor (TKI)
• Head & Neck Squamous Cell Carcinoma (HNSCC):
- I/O Naive HNSCC:
--Patients with HNSCC with no more than 3 prior lines of therapy; must have received a prior platinum-containing regimen and have not been previously treated with any anti-PD1/L1 agents in single agent/combinations
- I/O pre-treated HNSCC:
--Patients with HNSCC with no more than 2 prior lines of therapy; must have received a prior platinum-containing regimen and have been
pretreated with an anti-PD-1/PD-L1 as a single agent or in combinations
• Cutaneous Melanoma
- Patients must previously have received at least 1 and no more than 2 prior lines of therapy
- BRAF V600E wild type patients: must have received anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy
BRAF V600E mutant patients: must have received prior anti-PD-1/PDL1 single-agent, or in combination with anti-CTLA-4 therapy. In addition,subjects must have received prior BRAF V600E inhibitor therapy, either single-agent or in combination with a MEK inhibitor
• Diffuse Large B-Cell Lymphoma (DLBCL):
- Patients with DLBCL should be limited to those with no available therapies of proven clinical benefit
- Patient should have had prior autologous hematopoietic stem cell transplantation or determined to be ineligible for auto-HSCT.
• Non-Small Cell Lung Cancer (NSCLC):
- Patients with NSCLC must have received a prior platinum-based combination
- For patients with NSCLC, EGFR mutation with exon 19 deletion or L858R mutation (Exon 21) or anaplastic lymphoma receptor tyrosine
kinase (ALK) rearrangement positive must have failed prior Tyrosinekinase inhibitor (TKI) therapy
- Patients with EGFR positive NSCLC with a T790M mutation must have progressed on osimertinib or discontinued due to toxicity
4 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 cutanous melanoma, I/O pre-treated
5 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. |
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E.4 | Principal exclusion criteria |
- 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 2 or 3 prior lines of therapy as indicated for each tumor type in the inclusion criteria 4
- 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At protocol define timepoints until End of study. |
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E.5.2 | Secondary end point(s) |
- ORR, DCR, DoR, PFS, 2 years Overall Survival rate
- Frequency, severity and seriousness of AEs, laboratory abnormalities and other safety parameters. Dose interruptions, reductions and dose intensity.
- Change from baseline in TILs
- Plasma concentration time profiles of NIR178, NJI765 and PK parameters. Serum concentration time profiles of PDR001 and PK parameters.
- Presence and/or concentration of anti-PDR001 antibodies
- Frequency, severity and seriousness of DLTsl AEs, laboratory abnormalities and other safety parameters. Plasma concentration time profiles of NIR178 and PK parameters. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At protocol define timepoints until End of study. |
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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 | No |
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) | No |
E.7.1.1 | First administration to humans | No |
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 | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Australia |
Austria |
Belgium |
Czech Republic |
France |
Germany |
Italy |
Japan |
Netherlands |
Singapore |
Spain |
Switzerland |
Taiwan |
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
|
The study will end when all patients have completed the treatment period and 150-day safety follow-up, and at least 80% of patients have completed at least 24 months of survival follow up from start of study therapy. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 4 |