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Clinical Trial 19228

Cancer Type: Thoracic
Interventions:NIR178; Not Applicable; PDR001 (Spartalizumab)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Alberto Chiappori

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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

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.

Objective

Primary: 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 several intermittent dosing schedules of NIR178 in combination with PDR001 in NSCLC. Part 3: To evaluate efficacy of intermittent dosing schedule of NIR178 in NSCLC and another tumor type. Secondary: - To assess efficacy of NIR178+PDR001 in select advanced solid tumors and lymphoma. - To assess the safety and tolerability of the NIR178 and PDR001 combination. - To characterize changes in the immune infiltrate in tumors. - To characterize the pharmacokinetics (PK) of NIR178, its metabolite NJI765 and PDR001 in combination. - To assess immunogenicity of PDR001. Exploratory: - To assess the pharmacodynamic (PD) effect of NIR178 alone and in combination with PDR001 in tumor tissue and peripheral blood. - To assess potential predictors of efficacy of NIR178 in combination with PDR001.

Inclusion Criteria

  • Male or female patients 18 years of age or older.
  • 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) cancer, diffuse large B-cell lymphoma (DLBCL), microsatellite stable colorectal cancer (MSS CRC), triple negative breast cancer (TNBC) or cutaneous melanoma. Patients with colorectal cancer must have microsatellite stable (MSS) disease as detected by PCR-based assay or loss of mismatch repair (MMR) protein expression by immunohistochemistry and confirmed RAS genotype by standard testing of tumor specimen based on laboratory data. Patients with unresectable or metastatic cutaneous melanoma with confirmed BRAF V600E status by standard testing of tumor specimen by local available laboratory data.
  • Part 2: histologically confirmed diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant histology. Patients should have confirmed EGFR and ALK genotype when clinically indicated and performed per standard testing of tumor specimen based on local laboratory data.
  • 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 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.
  • Part 1 - 3: 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 cutaneous melanoma and I/O pre-treated HNSCC), unless considered inappropriate for the patient (e.g., safety concern, label contraindication). Additional criteria apply.
  • Patients with DLBCL should be limited to those with no available therapies of proven clinical benefit.
  • Should have had prior autologous hematopoietic stem cell transplantation (auto-HSCT) or determined to be ineligible for auto-HSCT.
  • Must not have received prior immunotherapy (previous immune checkpoint inhibitors; single agent and/or combination therapy with anti-CTLA-4, anti-PD-anti-PD-L1), with the exception of cutaneous melanoma, I/O pre-treated HNSCC, NSCLC patients enrolled in part 3 and Japanese safety run-in part.
  • 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 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 2 or 3 prior lines of therapy (as indicated for each tumor type).
  • 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 treatment.
  • Other protocol-defined exclusion criteria may apply.