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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03207867




Registration number
NCT03207867
Ethics application status
Date submitted
19/06/2017
Date registered
5/07/2017
Date last updated
9/09/2020

Titles & IDs
Public title
A Phase 2 Study of NIR178 in Combination With PDR001 in Patients With Solid Tumors and Non-Hodgkin Lymphoma
Scientific title
A Phase 2, Multi-center, Open Label Study of NIR178 in Combination With PDR001 in Patients With Selected Advanced Solid Tumors and Non-Hodgkin Lymphoma
Secondary ID [1] 0 0
2017-000241-49
Secondary ID [2] 0 0
CNIR178X2201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
NSCLC, Non Small Cell Lung Cancer 0 0
RCC, Renal Cell Cancer 0 0
Pancreatic Cancer 0 0
Urothelial Cancer 0 0
Head and Neck Cancer 0 0
DLBCL, Diffused Large B Cell Lymphoma 0 0
MSS, Microsatellite Stable Colon Cancer 0 0
TNBC, Triple Negative Breast Cancer 0 0
Melanoma 0 0
mCRPC, Metastatic Castration Resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NIR178
Treatment: Drugs - PDR001

Experimental: NIR178 + PDR001 - Part 1: all patients will receive NIR178 continuously in combination with PDR001 400mg every 4 weeks. The part 1 will enroll 8 different tumor types.

Experimental: NIR178 BID Intermittent + PDR001 - Three different dosing schedules of NIR178 will be explored.

Experimental: Part 3 - Initiation of part 3 will depend on results from parts 1 and 2.

Experimental: Japanese safety run-in part - Two different dosing schedules of NIR178 will be explored.


Treatment: Drugs: NIR178
NIR178, a new, non-xanthine based compound, is a potent oral adenosine A2a receptor against antagonist being developed by Novartis.

Treatment: Drugs: PDR001
PDR001 is a human monoclonal antibody (MAb) administered day 1 of each cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determine the overall response rate - Response assessed by RECIST v1.1 (for solid tumors), Cheson (for DLBCL) or PCWG3 criteria (for mCRPC)
Timepoint [1] 0 0
Every 8 weeks for first 40 weeks
Primary outcome [2] 0 0
Determine the overall response rate - Response assessed by RECIST v1.1 (for solid tumors), Cheson (for DLBCL) or PCWG3 criteria (for mCRPC)
Timepoint [2] 0 0
Every 12 weeks after the first 40 weeks until disease progression or study discontinuation (an average of 6 months)
Primary outcome [3] 0 0
Determine the overall response rate - Response assessed by RECIST v1.1 (for solid tumors), Cheson (for DLBCL), or PCWG3 criteria (for mCRPC)
Timepoint [3] 0 0
Baseline
Secondary outcome [1] 0 0
Determine the disease control rate (DCR) - Proportion of patients with a best overall response of CR or PR or SD
Timepoint [1] 0 0
Baseline
Secondary outcome [2] 0 0
Determine the duration of response (DoR) - Time from first documented response to disease progression
Timepoint [2] 0 0
Baseline
Secondary outcome [3] 0 0
Determine the overall survival rate (OR) - Time from start of treatment to date of death due to any reason
Timepoint [3] 0 0
Every 12 weeks until end of study for at least 24 months from the start date of the study treatment
Secondary outcome [4] 0 0
Progression free survival (PFS) - Time from start of treatment to date of the first documented progression or death in months
Timepoint [4] 0 0
Baseline
Secondary outcome [5] 0 0
Safety and tolerability of the NIR178 and PDR001 combination - Type, frequency, and severity of AEs and SAEs;
Frequency of dose interruptions, reductions and discontinuation, Dose intensity
Timepoint [5] 0 0
Date of consent to end of study (An average of 24 months)
Secondary outcome [6] 0 0
Characterize changes in the immune infiltrate in tumors - Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Timepoint [6] 0 0
Screening
Secondary outcome [7] 0 0
Presence and/or concentration of anti-PDR001 antibodies - Presence and/or concentration of anti-PDR001 antibodies
Timepoint [7] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [8] 0 0
Pharmacokinetics: Area under plasma concentration versus time curve (AUC) (NIR178) - Plasma concentration time profiles of NIR178 and its metabolites
Timepoint [8] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [9] 0 0
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) (PDR001) - Plasma concentration time profiles of PDR001
Timepoint [9] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [10] 0 0
Plasma concentration Vs Time profiles (NIR178) - Plasma concentration time profiles of NIR178
Timepoint [10] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [11] 0 0
Plasma concentration Vs Time profiles (PDR001) - Plasma concentration time profiles of PDR001
Timepoint [11] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [12] 0 0
Peak plasma concentration- Cmax (NIR178) - Plasma concentration time profiles of NIR178
Timepoint [12] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [13] 0 0
Peak plasma concentration- Cmax (PDR001) - Plasma concentration time profiles of PDR001
Timepoint [13] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [14] 0 0
Time of maximum concentration observed- Tmax (NIR178) - Plasma concentration time profiles of NIR178
Timepoint [14] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [15] 0 0
Time of maximum concentration observed- Tmax (PDR001) - Plasma concentration time profiles of PDR001
Timepoint [15] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [16] 0 0
Determine the disease control rate (DCR) - Proportion of patients with a best overall response of CR or PR or SD
Timepoint [16] 0 0
Every 8 weeks for first 40 weeks
Secondary outcome [17] 0 0
Determine the disease control rate (DCR) - Proportion of patients with a best overall response of CR or PR or SD
Timepoint [17] 0 0
Every 12 weeks after the first 40 weeks until disease progression
Secondary outcome [18] 0 0
Determine the duration of response (DoR) - Time from first documented response to disease progression
Timepoint [18] 0 0
Until study discontinuation (an average of 6 months)
Secondary outcome [19] 0 0
Determine the duration of response (DoR) - Time from first documented response to disease progression
Timepoint [19] 0 0
Every 8 weeks for first 40 weeks
Secondary outcome [20] 0 0
Progression free survival (PFS) - Time from start of treatment to date of the first documented progression or death in months
Timepoint [20] 0 0
Until study discontinuation (an average of 6 months)
Secondary outcome [21] 0 0
Progression free survival (PFS) - Time from start of treatment to date of the first documented progression or death in months
Timepoint [21] 0 0
Every 8 weeks for first 40 weeks
Secondary outcome [22] 0 0
Characterize changes in the immune infiltrate in tumors - Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Timepoint [22] 0 0
Cycle 6 Day 1
Secondary outcome [23] 0 0
Characterize changes in the immune infiltrate in tumors - Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Timepoint [23] 0 0
Cycle 1 Day 8
Secondary outcome [24] 0 0
Characterize changes in the immune infiltrate in tumors - Change from baseline in TILs by immunohistochemistry (IHC) (such as CD8)
Timepoint [24] 0 0
Cycle 3 Day 1
Secondary outcome [25] 0 0
Presence and/or concentration of anti-PDR001 antibodies - Presence and/or concentration of anti-PDR001 antibodies
Timepoint [25] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [26] 0 0
Pharmacokinetics: Area under plasma concentration versus time curve (AUC) (NIR178) - Plasma concentration time profiles of NIR178 and its metabolites
Timepoint [26] 0 0
End of treatment and as needed (an average of 6 months)
Secondary outcome [27] 0 0
Plasma concentration Vs Time profiles (NIR178) - Plasma concentration time profiles of NIR178
Timepoint [27] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [28] 0 0
Plasma concentration Vs Time profiles (PDR001) - Plasma concentration time profiles of PDR001
Timepoint [28] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [29] 0 0
Peak plasma concentration- Cmax (NIR178) - Plasma concentration time profiles of NIR178
Timepoint [29] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [30] 0 0
Peak plasma concentration- Cmax (PDR001) - Plasma concentration time profiles of PDR001
Timepoint [30] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [31] 0 0
Time of maximum concentration observed- Tmax (NIR178) - Plasma concentration time profiles of NIR178
Timepoint [31] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [32] 0 0
Time of maximum concentration observed- Tmax (PDR001) - Plasma concentration time profiles of PDR001
Timepoint [32] 0 0
Starting from the first dose of study treatment to Cycle 6 Day 1
Secondary outcome [33] 0 0
Determine the disease control rate (DCR) - Proportion of patients with a best overall response of CR or PR or SD
Timepoint [33] 0 0
Until study discontinuation (an average of 6 months)
Secondary outcome [34] 0 0
Determine the duration of response (DoR) - Proportion of patients with a best overall response of CR or PR or SD
Timepoint [34] 0 0
Every 12 weeks after the first 40 weeks until disease progression
Secondary outcome [35] 0 0
Progression free survival (PFS) - Time from start of treatment to date of the first documented progression or death in months
Timepoint [35] 0 0
Every 12 weeks after the first 40 weeks until disease progression

Eligibility
Key inclusion criteria
- Male or female patients =18 years of age. For Japan only: written consent is necessary
both from the patient and his/her legal representative if he/she is under the age of
20 years.

- 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), melanoma, metastatic
castration resistant prostate cancer (mCRPC) 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 selected
advanced/metastatic malignancies should part 3 be opened for enrollment

- Patient (except for those participating in Japanese safety run-in) 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.

- Safety run-in part in Japanese patients can enroll any tumor type included in part 1
and 2.

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.

- Part 1 - 3 only: 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 (with the exception of
IO-pretreated cutaneous melanoma, HNSCC and RCC), unless considered inappropriate for the
patient (e.g. safety concern, label contraindication): Patients with NSCLC must have
received a prior platinum-based combination. Patients with EGFR positive NSCLC with a T790M
mutation must have progressed on osimertinib or discontinued due to toxicity.

Patients with head and neck cancer must have received a prior platinum-containing regimen.

Patients with bladder cancer must have received a prior platinum-containing regimen or be
ineligible for cisplatin.

Patients with renal cell carcinoma must have received a prior VEGF tyrosine kinase
inhibitor (TKI).

Patients with MSS colorectal cancer must have received (or be intolerant to) prior therapy
with fluoropyrimidine-oxaliplatin- and irinotecan- based regimens.

Patients with triple negative breast cancer must have received a prior taxane-containing
regimen.

Patients with DLBCL should be limited to those with no available therapies of proven
clinical benefit Patients should have had prior autologous hematopoietic stem cell
transplantation (auto-HSCT) or determined to be ineligible for auto-HSCT.

Patients with melanoma:

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/PD-L1 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

Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC):

- Of the 1-3 prior lines of therapy, patients must have received and failed at least one
line of treatment after emergence of castration resistant 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 and Japanese safety run-in
part.

- 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 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 except for Japanese safety run-in part.

- History of interstitial lung disease or non-infectious pneumonitis

- Participation in another clinical study with an investigational product during the
last 21 days prior to starting on treatment.

- Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For
cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas,
6 weeks is indicated as washout period. For patients receiving anticancer
immunotherapies, 4 weeks is indicated as the washout period. GnRH therapy to maintain
effective testosterone suppression levels is allowed for mCRPC patients.

Other protocol-defined exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Blacktown
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin
Country [7] 0 0
Austria
State/province [7] 0 0
Salzburg
Country [8] 0 0
Belgium
State/province [8] 0 0
Liege
Country [9] 0 0
Czechia
State/province [9] 0 0
Czech Republic
Country [10] 0 0
France
State/province [10] 0 0
Marseille
Country [11] 0 0
Germany
State/province [11] 0 0
Essen
Country [12] 0 0
Germany
State/province [12] 0 0
Koeln
Country [13] 0 0
Italy
State/province [13] 0 0
MI
Country [14] 0 0
Italy
State/province [14] 0 0
Napoli
Country [15] 0 0
Japan
State/province [15] 0 0
Tokyo
Country [16] 0 0
Netherlands
State/province [16] 0 0
Rotterdam
Country [17] 0 0
Singapore
State/province [17] 0 0
Singapore
Country [18] 0 0
Spain
State/province [18] 0 0
Catalunya
Country [19] 0 0
Switzerland
State/province [19] 0 0
St. Gallen
Country [20] 0 0
Taiwan
State/province [20] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in
combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL)
and further explore schedule variations of NIR178 to optimize immune activation through
inhibition of A2aR.
Trial website
https://clinicaltrials.gov/show/NCT03207867
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
Novartis.email@novartis.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03207867