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BRIEF TITLE: Study of NIR178 in Combination With PDR001 in Patients With Selected Advanced Bladder Cancer

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

  • Org Study ID: CNIR178X2201
  • Secondary ID: 2017-000241-49
  • NCT ID: NCT03207867
  • NCT Alias:
  • Sponsor: Novartis Pharmaceuticals - Industry
  • Source: Novartis

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.

Detailed Description

The study has three parts: part 1: Multi-arm Bayesian adaptive signal finding design in solid
tumors and diffuse large B cell lymphoma (DLBCL); part 2: NIR178 schedule exploration in
NSCLC; part 3: Further evaluation of intermittent or continuous dosing schedules of NIR178 in
combination with PDR001 in additional tumor types, if part 2 identifies an intermittent or
continuous dosing schedule of NIR178 as warranting further exploration. In addition, a
separate safety run-in part will be conducted in Japan in order to adequately characterize
the safety and pharmacokinetic profiles of NIR178 as a single-agent and in combination with

Parts 1 and 2 and the safety run-in in Japan will enroll in parallel. Part 3 will be opened
based on the results from part 1 and part 2 and may enroll in parallel with Part 1.

Patients enrolled in this study will receive NIR178 either BID continuously or based on the
assigned intermittent schedule within 60 minutes prior to PDR001 infusion. PDR001 will be
administered via IV infusion over 30 minutes once every 4 weeks. Each treatment cycle is 28
days. Patients enrolled in the Japanese safety run-in part will receive NIR178 as single
agent for the first cycle (28 days). If the patients complete cycle 1 without experiencing
DLTs, they will initiate combination therapy with PDR001 starting cycle 2 onwards, and
continue at the same dose of NIR178. An additional cohort in the Japanese safety run-in part
of the study will receive NIR178 in combination with PDR001 starting with Cycle 1. If the
patients complete cycle 1 without experiencing DLTs, they will continue to receive
combination treatment.

Patients will receive treatment with the combination until disease progression (assessed by
investigator per immune-related response criteria (iRECIST) or Cheson 2014, unacceptable
toxicity, death or discontinuation from study treatment for any other reason (e.g.,
withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the
investigator), otherwise known as End of Treatment.

Overal Status Start Date Phase Study Type
Recruiting August 28, 2017 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Determine the overall response rate

Primary Outcome 1 - Time Frame: Every 8 weeks for first 40 weeks

Primary Outcome 2 - Measure: Determine the overall response rate

Primary Outcome 2 - Time Frame: Every 12 weeks after the first 40 weeks until disease progression or study discontinuation (an average of 6 months)

Primary Outcome 3 - Measure: Determine the overall response rate

Primary Outcome 3 - Time Frame: Baseline


  • NSCLC, Non Small Cell Lung Cancer
  • RCC, Renal Cell Cancer
  • Pancreatic Cancer
  • Urothelial Cancer
  • Head and Neck Cancer
  • DLBCL, Diffused Large B Cell Lymphoma
  • MSS, Microsatellite Stable Colon Cancer
  • TNBC, Triple Negative Breast Cancer
  • Melanoma
  • mCRPC, Metastatic Castration Resistant Prostate Cancer


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. Part 3 will be opened to further assess TNBC
patients with a PD-L1 SP-142 IC score of 0 (<1%). A second tumor group will be
considered for Part 3 after completion of Part 1.

- 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,
2 and 3.

The collection of recent sample is permitted under the following conditions (both must be

Biopsy was collected ≤ 6 months before 1st dose of study treatment and available at the

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:. Part 1: must have received a prior
taxane-containing regimen Part 3: should have received no more than 2 prior lines of
therapy including taxane-based chemotherapy and should have a known PD-L1 status as per
local available testing as determined by VENTANA PD-L1 SP142 Assay with IC score of 0 (<1%)
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

- 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.

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

- 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

- 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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Novartis Pharmaceuticals

Phone: 1-888-669-6682



Facility Status Contact
University of California, Los Angeles
Santa Monica, California 90904
United States
Recruiting Branden Brooks
H Lee Moffitt Cancer Center and Research Institute Inc
Tampa, Florida 33612
United States
Recruiting Mark Kuhns
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland 21205
United States
Recruiting Twyla Robinson
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43212
United States
Recruiting Mollie Alter
MD Anderson Cancer Center/University of Texas
Houston, Texas 77030
United States
Active, not recruiting
The University of Wisconsin
Madison, Wisconsin 53792
United States
Recruiting Samanike Hengst
Novartis Investigative Site
Caba, Buenos Aires C1426ANZ
Novartis Investigative Site
Blacktown, New South Wales 2148
Active, not recruiting
Novartis Investigative Site
Salzburg, 5020
Novartis Investigative Site
Liege, 4000
Novartis Investigative Site
Brno, Czech Republic 656 53
Novartis Investigative Site
Marseille, 13273
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Koeln, 50937
Novartis Investigative Site
Milano, MI 20133
Novartis Investigative Site
Napoli, 80131
Novartis Investigative Site
Koto ku, Tokyo 135 8550
Novartis Investigative Site
Rotterdam, 3075 EA
Novartis Investigative Site
Singapore, 169610
Novartis Investigative Site
Barcelona, Catalunya 08035
Novartis Investigative Site
St. Gallen, 9007
Novartis Investigative Site
Taipei, 10002