Brief Title: A Phase 2 Study of NIR178 in Combination With PDR001 in Patients With Solid Tumors and Non-Hodgkin Lymphoma

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Determine the overall response rate

Primary Outcome 1 - Timeframe: Every 8 weeks for first 40 weeks

Primary Outcome 2 - Measure: Determine the overall response rate

Primary Outcome 2 - Timeframe: 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 - Timeframe: Baseline

CONDITION

• 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

ELIGIBILITY

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 met):
Biopsy was collected ≤ 6 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:. 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 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.
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

- 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

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Overall Contact

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Phone: 1-888-669-6682, +41613241111

Email: Novartis.email@novartis.com

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