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.
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
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.
- 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
- 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
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.
- 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.