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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 four 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 dosing schedules of NIR178 in combination
with PDR001 in additional tumor types, if part 2 identifies an intermittent dosing schedule
of NIR178 as warranting further exploration; part 4: 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.

Parts 1, 2 and 4 will enroll in parallel. Part 3 will be opened based on the results from
part 2.

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.

Patients will receive treatment with the combination until disease progression (assessed by
investigator per immune-related response criteria (irRC) 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 April 26, 2016 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


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) or

- 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 (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.

o Part 4: 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

- 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, specifically including
the following, unless considered inappropriate for the patient (e.g. safety concern, label

- 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

- 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

o Patients should have had prior autologous hematopoietic stem cell transplantation
(auto-HSCT) or determined to be ineligible for auto-HSCT.

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.

Other protocol-defined inclusion criteria may apply.

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

- 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

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



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