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SNCTP000002350 | NCT03207867 | BASEC2017-01310

Studie zu NIR178 in Kombination mit PDR001 bei Patienten mit ausgewählten fortgeschrittenen soliden Tumoren und Non-Hodgkin-Lymphom

Data source: BASEC (Imported from 28.03.2024), WHO (Imported from 20.03.2024)
Changed: Feb 12, 2024, 7:28 AM
Disease category: Non-Hodgkin Lymphoma, Other Cancer, Pancreatic Cancer, Bladder Cancer, Colon and Rectal Cancer, Breast Cancer, Melanoma

Brief description of trial (Data source: BASEC)

In dieser klinischen Studie soll untersucht werden, ob die Kombinationstherapie mit NIR178 und PDR001 bei Patienten mit fortgeschrittenem bzw. metastatischem Krebs wirksam und sicher ist. NIR178 und PDR001 sind Medikamente, die Immunsystem zur Bekämpfung des Tumors aktivieren. PDR001 ist eine intravenöse Infusion und NIR178 sind Kapseln zum Schlucken. Sie sind noch von keiner Gesundheitsbehörde der Welt zugelassen. In der Studie werden drei verschieden Dosierungsschemen untersucht, um das sicherste und wirksamste Dosierungsschema zu ermitteln. Es werden rund 280 Patienten weltweit teilnehmen, davon 10-15 in der Schweiz.

Health conditions investigated(Data source: BASEC)

Fortgeschrittener Lymphom (diffuser grosszelliger B-Zell-Lymphom) oder fortgeschrittene solide Tumoren wie Nierenzellkarzinom, Bauchspreicheldrüsenkrebs, Urothelkarzinom, Kopf- und Halskarzinom, , Kolonkarzinom (mit stabilen Mikrosatelliten), Brustkrebs (dreifachnegativ), nichtkleinzelliger Lungenkrebs oder Melanom

Health conditions (Data source: WHO)

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

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Die Studie besteht aus drei Teilen:

Teil 1: Patienten mit ausgewählten Tumoren (s. oben) werden in diesen Teil der Studie eingeschlossen. Sie werden zweimal täglich zwei Kapseln NIR178 nehmen und erhalten alle vier Wochen eine intravenöse Infusion mit PDR001.

Teil 2: Patienten mit nichtkleinzelligem Lungenkrebs werden in diesen Teil der Studie eingeschlossen. Nach dem Zufallsprinzip werden sie einem von drei Dosierungsschema zugeteilt, um das sicherste und wirksamste Dosierungsschema zu ermitteln:
• Dosierungsschema 1: Zwei Kapseln NIR178 zweimal täglich, kontinuierlich in Kombination mit PDR001, intravenös, alle 4 Wochen.
• Dosierungsschema 2: Zwei Kapseln NIR178 zweimal täglich zwei Wochen lang, gefolgt von zwei Wochen Pause, in Kombination mit PDR001, intravenös, alle 4 Wochen.
• Dosierungsschema 3: Zwei Kapseln NIR178 zweimal täglich eine Woche lang, gefolgt von einer Woche Pause, in Kombination mit PDR001, intravenös, alle 4 Wochen.

Teil 3 wird dann gestartet, sobald die Teile 1 und 2 abgeschlossen sind und das beste Dosierungsschema fest steht. In diesem Teil werden die Sicherheit, Wirksamkeit und Immunveränderungen der Behandlung bei zwei Tumorarten je nach Ergebnissen aus Teilen 1 und 2 untersucht.

Interventions (Data source: WHO)

Drug: NIR178;Drug: PDR001

Criteria for participation in trial (Data source: BASEC)

- Männliche oder weibliche Patienten älter als 18 Jahre
- Patienten mit diffusem grosszelligen B-Zell-Lymphom oder fortgeschrittenen soliden Tumoren wie Nierenzellkarzinom, Bauchspreicheldrüsenkrebs, Urothelkarzinom, Kopf- und Halskarzinom, , Kolonkarzinom (mit stabilen Mikrosatelliten), Brustkrebs (dreifachnegativ), nichtkleinzelliger Lungenkrebs oder Melanom

Exclusion criteria (Data source: BASEC)

- Patienten, die Hirnmetastasen haben
- Patienten, die in letzten 2 Jahren eine Autoimmunerkrankung hatten
- Patienten, die unter einer chronisch-entzündlichen Darmerkrankung leiden

Inclusion/Exclusion Criteria (Data source: WHO)

Gender: All
Maximum age: N/A
Minimum age: 18 Years

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.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03207867

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT03207867
Further information on trial

Recruitment status

Terminated

Academic title (Data source: WHO)

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

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Part 1: Overall Response Rate (ORR);Part 2: Overall Response Rate (ORR);Part 3: Overall Response Rate (ORR)

Secundary end point (Data source: WHO)

Overall Response Rate (ORR) by iRECIST;Best Prostate-specific antigen (PSA) change from baseline (only for mCRPC);Disease Control Rate (DCR);Duration of response (DoR);Progression Free Survival (PFS);2 year Overall Survival (OS) rate;Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs);Number of participants with dose interruptions and reductions of study treatments;Dose intensity of study treatments;Change from baseline in Tumor infiltrating lymphocytes (TILs);Peak concentration (Cmax) of NIR178, its metabolite NJI765 and PDR001;Time to peak concentration (Tmax) of NIR178, its metabolite NJI765 and PDR001;Area under the curve (AUC) of NIR178, its metabolite NJI765 and PDR001;Number of participants with anti-PDR antibodies;Incidence of Dose-Limiting Toxicities (DLTs) (Japanese Safety run-in only)

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

St. Gallen

Countries (Data source: WHO)

Argentina, Australia, Austria, Belgium, Czechia, France, Germany, Italy, Japan, Netherlands, Singapore, Spain, Switzerland, Taiwan, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Janine Woytschak
+41 79 500 93 56
janine.woytschak@novartis.com

Contact for general information (Data source: WHO)

Novartis Pharmaceuticals
1-888-669-6682
Novartis.email@novartis.com

Contact for scientific information (Data source: WHO)

Novartis Pharmaceuticals
1-888-669-6682
Novartis.email@novartis.com

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Ethikkommission Ostschweiz (EKOS)

Date of authorisation by the ethics committee

11.09.2017

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2017-01310

Secondary ID (Data source: WHO)

2017-000241-49
CNIR178X2201
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