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

  • STATUS
    Recruiting
  • End date
    Jun 16, 2023
  • participants needed
    376
  • sponsor
    Novartis Pharmaceuticals
Updated on 8 May 2021
cancer
tyrosine
monoclonal antibodies
measurable disease
carcinoma
breast cancer
melanoma skin
kinase inhibitor
BRAF
oxaliplatin
fluoropyrimidine
EGFR
irinotecan
pd-l1
cancer chemotherapy
solid tumour
triple negative breast cancer
mek inhibitor
squamous cell carcinoma of head and neck
bladder cancer
vascular endothelial growth factor
taxane
osimertinib
cytotoxic t-lymphocyte antigen 4
malignant melanoma of skin
braf v600e mutation

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.

Description

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 PDR001.

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 combination treatment.

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.

Details
Condition Pancreatic Cancer, Non-Small Cell Lung Cancer, Pancreatic disorder, melanoma, skin cancer, Neoplasm of unspecified nature of digestive system, head and neck cancer, Pancreatic Disorders, Metastatic Melanoma, Urothelial Cancer, Islet Ce417ll Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, Malignant Melanoma, Digestive System Neoplasms, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, cancer of the head and neck, cancer of the pancreas, pancreatic cancers, cancer, pancreatic, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer, RCC, Renal Cell Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, mCRPC, Metastatic Castration Resistant Prostate Cancer
Treatment PDR001, NIR178
Clinical Study IdentifierNCT03207867
SponsorNovartis Pharmaceuticals
Last Modified on8 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: DLBCL, Diffused Large B Cell Lymphoma or mCRPC, Metastatic Castration Resistant Prostate Cancer or Digestive System Neoplasms or TNBC, Triple Negative...?
Do you have any of these conditions: Malignant Melanoma or Non-Small Cell Lung Cancer or DLBCL, Diffused Large B Cell Lymphoma or Metastatic Melanoma or pancreatic cancers or Digestive Sy...?
Do you have any of these conditions: pancreatic cancers or Metastatic Melanoma or cancer, pancreatic or DLBCL, Diffused Large B Cell Lymphoma or Malignant Melanoma or Islet Ce417ll Cancer...?
Do you have any of these conditions: Pancreatic Cancer or cancer of the pancreas or Islet Ce417ll Cancer or DLBCL, Diffused Large B Cell Lymphoma or Neoplasm of unspecified nature of dige...?
Do you have any of these conditions: melanoma or mCRPC, Metastatic Castration Resistant Prostate Cancer or head and neck cancer or Digestive System Neoplasms or Metastatic Melanoma or DLB...?
Do you have any of these conditions: cancer, pancreatic or mCRPC, Metastatic Castration Resistant Prostate Cancer or Neoplasm of unspecified nature of digestive system or TNBC, Triple Neg...?
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
Patients with melanoma
transplantation (auto-HSCT) or determined to be ineligible for auto-HSCT
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
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