Advanced solid tumor (NSCLC, RCC, pancreatic cancer, urothelial cancer, head and neck squamous cell carcinoma, microsatellite stable colorectal cancer, triple negative breast cancer, cutaneous melanoma) and diffuse large B-cell lymphoma (DLBCL)
Conditions
Interventions
Part 1: 13 groups (some of which in subgroups based on mutation status or prior treatment), and diffuse large B cell lymphoma (DLBCL) with continuous dosing of NIR178 in combination with PDR001.
Part
Sponsors
Novartis Pharma. K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female patients over 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 squamous cell carcinoma (HNSCC), diffuse large B-cell lymphoma (DLBCL), microsatellite stable colorectal cancer (MSS CRC), triple negative breast cancer (TNBC), cutaneous melanoma or mCRPC 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 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. In addition, a separate safety run-in part will be conducted for patients in Japan in order to evaluate safety and pharmacokinetics of NIR178 as a single agent and NIR178 in combination with PDR001 prior to their participation in different parts of this phase II study, as recommended by the Japanese Health Authority. This Japanese safety run-in part will enroll separately from the phase II study in the rest of the world (RoW). 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. Based on emerging data from Part 1, Part 2 and latest scientific literature along with discussion between Novartis and study investigators, one or two tumor groups will be further explored in Part 3. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
Exclusion criteria
Exclusion criteria: Ongoing or prior treatment with A2aR inhibitors. Patients previously treated with A2aR inhibitors for non-oncologic indications (e.g. Parkinsons disease) may be considered for enrollment on a case by case basis. 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. Gonadotropin-releasing hormone (GnRH) therapy to maintain effective testosterone suppression levels is allowed for mCRPC patients. 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 interstitial lung disease or non-infectious pneumonitis History of another primary malignancy except Active or prior documented autoimmune disease within the past 2 years. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. More than 2 or 3 prior lines of therapy (as indicated above for each tumor group), except for Japanese safety run-in part.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety efficacy Part 1:To evaluate the efficacy of NIR178 and PDR001 combination in patients with selected advanced solid tumors and diffuse large B cell lymphoma (DLBCL). Part 2: To assess the efficacy of several intermittent dosing schedules of NIR178 in combination with PDR001 in NSCLC. Part 3: To further evaluate efficacy of the best performing dosing schedule of NIR178 in one or two tumor groups selected from Part 1 and Part 2. The additional tumor groups will be selected based on the emerging data from Part 1 and Part 2. | — |
Countries
Asia except Japan, Europe, Japan, North America, Oceania
Contacts
Public ContactSanae Moizumi
Novartis Pharma. K.K.
Outcome results
None listed