Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Durvalumab

Adenosine

Antineoplastic Agents, Immunological

Participants will receive monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter will continue to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until will derive clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.

Participants will receive combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.

In Module 1, participants will receive AZD4635 75 mg capsule orally QD for first 14 days and thereafter will continue to receive 75 mg orally QD Q4W.

In Module 2, participants will receive AZD4635 50 mg / 75 mg capsule orally QD Q2W of 28-day cycle for the first 4 doses and Q4W thereafter.

In both modules, participants will receive treatment until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.

AZD4635

In Module 2, participants will receive oleclumab 1500 mg IV (solution for infusion after dilution, 50 mg/mL) Q2W of 28-day cycle for the first 4 doses and Q4W thereafter until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.

Oleclumab

In Module 1 after monotherapy of AZD4635, participants will receive durvalumab 1500 mg IV (solution for infusion after dilution, 50 mg/mL) Q4W until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.

This is an open-label Phase II modular study in participants with prostate cancer which will assess safety, efficacy, and tolerability of AZD4635 in combination with other therapeutic agents in different treatment arms (referred to as modules).

Combinations to be studied include: 1) Module 1: AZD4635 plus durvalumab; 2) Module 2: AZD4635 plus oleclumab.

This is an open-label Phase II modular study in participants with prostate cancer which will assess safety, efficacy, and tolerability of AZD4635 in combination with other therapeutic agents in different treatment arm (referred to as modules).

Combinations to be studied include: 1) Module 1: AZD4635 plus durvalumab; 2) Module 2: AZD4635 plus oleclumab.

All participants will be allocated into a module using an Interactive Web Response System (IWRS). Randomization will occur when patients meet eligibility criteria for two or more modules that are currently recruiting. If participants only meet the criteria for one currently recruiting module, they will be allocated to that module without randomization taking place.

The primary objective of the clinical study is to evaluate the efficacy of each combination therapy by: 1) assessing the objective response rate (ORR) of participants with measurable disease (response will be determined by Response Evaluation Criteria in Solid Tumours \[RECIST 1.1\]); 2) assessing the prostate-specific antiget (PSA) confirmed response rate of each combination therapy (PSA confirmed response rate is defined as the proportion of participants with a reduction in the PSA level of ≥50% measured from baseline to the lowest post-baseline PSA result measured twice, at least 3 weeks apart by the Prostate Cancer Working Group 3 criteria \[PCWG3\]).

The safety endpoints include assessment of adverse events and serious adverse events, physical examinations, vital signs, and collection of clinical chemistry/hematology parameters

There will be approximately 30 PSA evaluable participants in each module, and approximately 20 participants will have RECIST measurable disease at baseline in each module. If any of the required participants for PSA and/or ORR are not evaluable for PSA response or tumor response, respectively, they may be replaced at the sponsor's discretion.

This study will enroll only male participants because the condition being studied is metastatic castration-resistant prostate cancer.

An Open-label, Phase II Study of AZD4635 in Patients With Prostate Cancer

An Open-label, Multi-drug, Multi-center Phase II Combination Study of AZD4635 in Patients With Prostate Cancer

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

The confirmed objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines, assessed by computed tomography (CT) scan/ magnetic resonance imaging (MRI) scan/ positron emission tomography (PET) scan and bone scan. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.

A confirmed PSA response is defined as reduction in the PSA level of \>= 50% from baseline to the lowest post-baseline PSA results, measured twice, at least 3 weeks apart by the PCWG3 criteria.

The rPFS is defined as the time interval from the first dose of AZD4635 until the date of radiological disease progression (RECIST 1.1 for soft tissue lesions and PCWG3 criteria for bone lesions) or death (by any cause in the absence of progression) regardless of whether the participant withdrew from study therapy or received another anti-cancer therapy prior to progression. The progressive disease for soft lesions per RECIST 1.1 (assessed by CT/MRI/PET scan) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum in the study, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The progressive disease for bone lesions per PCWG3 is defined as at least 2 or more new metastatic bone lesions observed compared to baseline assessment (Day -28), with confirmation scan performed at least 6-week later.

The DoR is defined as the time from the date of first documented response (confirmed CR/PR) until date of documented progression or death in the absence of disease progression. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The DoR was estimated using Kaplan-Meier method.

The OS is defined as the time from date of first study dose until the date of death due to any cause. The median of OS was estimated using Kaplan-Meier method and CI was derived based on Brookmeyer-Crowley method.

The detection of the immunogenicity of monoclonal antibody to durvalumab was performed using a validated immunoassay method. Participants with positive ADA to durvalumab are reported.

The detection of the immunogenicity of monoclonal antibody to oleclumab was performed using a validated immunoassay method. Participants with positive ADA to oleclumab are reported.

Plasma concentrations of AZD4635 and its metabolites (SSP-005173 and SSP-005174) are reported.

Plasma concentration of durvalumab is reported.

Plasma concentration of oleclumab is reported.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Laboratory parameters included hematology, coagulation, clinical chemistry, and urinalysis. The CTCAE is a descriptive terminology is used for AE reporting. The CTCAE v5.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death related to AE. Participants with CTCAE v5.0 grade change in laboratory parameters from baseline (Day 1 before the start of study treatment) to Grade 3 or more are reported.

Vital signs assessment included body temperature, respiration rate, pulse rate, blood pressure, and weight. Participants with abnormal vital signs and/or abnormal physical examination reported as TEAEs are reported.

AstraZeneca

Participants received monotherapy of AZD4635 75 mg orally once daily (QD) for first 14 days and thereafter continued to receive 75 mg orally QD in combination with durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W) until derived clinical benefit as judged by the investigator, confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.

Module 1 (AZD4635 75 mg + Durvalumab 1500 mg)

Participants received combination therapy of AZD4635 (50 mg / 75 mg orally QD) and oleclumab 1500 mg IV (every 2 weeks of 28-day cycle for the first 4 doses and Q4W thereafter) until derived clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurred first.

Module 2 (AZD4635 50 / 75 mg + Oleclumab 1500 mg)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety analysis set included all participants who received at least one dose of study drug.

Global Clinical Lead

Tumor response analysis set included all participants who received at least one dose of study drug and had a baseline tumor assessment and measurable disease at baseline.

Percentage of Participants With Confirmed Objective Response Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

The PSA response analysis set included all participants who received at least one dose of study drug and had an abnormal baseline PSA data (\>= 1 ng/mL).

Percentage of Participants With Confirmed Prostate-specific Antigen (PSA) Response Per Prostate Cancer Working Group 3 (PCWG3) Criteria

Efficacy analysis set included all participants who received at least one dose of study drug and had a baseline tumor assessment.

Percentage of Participants With Radiological Progression Free Survival (rPFS) at 6 Months

Tumor response analysis set included all participants who received at least one dose of study drug and had a baseline tumor assessment (Day -28) and measurable disease at baseline. Participants who had confirmed CR/PR were analyzed for this outcome measure.

Duration of Response (DoR)

Overall Survival (OS)

Safety analysis set included all participants who received at least one dose of durvalumab and had at least one post dose ADA sample.

Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab

Safety analysis set included all participants who received at least one dose of oleclumab and had at least one post dose ADA sample.

Number of Participants With Positive ADA to Oleclumab

AZD4635 concentration

SSP-005173 concentration

SSP-005174 concentration

Pharmacokinetics (PK) analysis set included all participants who received at least one dose of AZD4635 and had at least 1 reportable PK concentration at Cycle 7.

Plasma Concentrations of AZD4635 and Its Metabolites (SSP-005173 and SSP-005174)

Pre-dose

End of infusion

The PK analysis set included all participants who received at least one dose of durvalumab and had at least 1 reportable PK concentration at Cycle 7. 'Number analyzed' denotes the number of participants evaluated for the specified time point.

Plasma Concentration of Durvalumab

10 minutes end of infusion

The PK analysis set included all participants who received at least one dose of oleclumab and had at least 1 reportable PK concentration at Cycle 7. 'Number analyzed' denotes the number of participants evaluated for the specified time point.

Plasma Concentration of Oleclumab

Any TEAEs

Any TESAEs

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Hemoglobin (low)

Leukocytes (low)

Lymphocytes (low)

Albumin

Alkaline Phosphatase

Gamma Glutamyl Transferase

Lipase

Sodium (low)

Number of Participants With Common Terminology Criteria for Adverse Events (CTCAE) Grade Change in Laboratory Parameters From Baseline to Grade 3 or More

Cachexia

Hypertension

Hypotension

Gait disturbance

Pyrexia

Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Lung Neoplasms

Pancreatic Neoplasms

Lymphoma

Triple Negative Breast Neoplasms

Melanoma

Carcinoma, Renal Cell

Head and Neck Neoplasms

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Carcinoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Skin Diseases

Breast Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Pancreatic Cancer

Lymphosarcoma

Renal Cell Carcinoma

B-cell Lymphoma

Gastrointestinal Agents

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Lactitol

Spartalizumab

Immune Checkpoint Inhibitors

Part 1: NIR178 continuously in combination with PDR001 400mg every 4 weeks. The part 1 enrolled 9 different tumor types.

Part 2: Three different dosing schedules of NIR178 twice daily (BID) including continuous and two intermittent in combination with PDR001

Further evaluation of optimal intermittent or continuous schedule of NIR178 in combination with PDR001 (if selected based on results of Part 2). A film-coated tablet of NIR178 was assessed.

Different dosing schedules of NIR178 were explored.

NIR178, a new, non-xanthine based compound, is a potent oral adenosine A2a receptor against antagonist being developed by Novartis.

NIR178 was administered orally twice daily (BID) as a capsule (Part 1, Part 2 and Japanese safety run-in) and as a film-coated table (Part 3). There were up to 3 dose levels assessed: 80, 160 and 240 mg. Three alternative dosing schedules were evaluated: continuous (Part 1, Part 2, Part 3, Japanese safety run-in), 2 weeks on/2 weeks off (Part 2) and 1 week on/1 week off (Part 2).

Each cycle consisted of 28 days.

NIR178

PDR001 is a human monoclonal antibody (MAb) administered on Day 1 of each cycle. PDR001 400 mg was administered via intravenous (i.v.) infusion over 30 minutes every 4 weeks (Q4W).

PDR001

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.

This is an open-label multi-part, phase II study evaluating the combination of NIR178 and PDR001 in patients with advanced solid tumors and diffuse large B cell lymphoma (DLBCL).

The study has three parts:

* Part 1: Multi-arm Bayesian adaptive signal finding design in solid tumors and diffuse large B cell lymphoma (DLBCL) with continuous dosing of NIR178 in combination with PDR001.
* Part 2: Exploration of continuous and intermittent NIR178 schedules in combination with PDR001 in patients with advanced non-small cell lung cancer (NSCLC).
* Part 3: Further evaluation of optimal intermittent or continuous schedule of NIR178 in combination with PDR001 (if selected based on results of Part 2). As of protocol amendment 6, Part 3 explored the safety and pharmacokinetics of the film-coated tablet (FCT) formulation of NIR178 continuous dosing in combination with PDR001 in tiple negative breast cancer (TNBC) patients.

In addition, a separate safety run-in part was conducted in Japan in order to adequately characterize the safety and pharmacokinetic profiles of NIR178 as a single-agent and in combination with PDR001.

Patients enrolled in this study received NIR178 either twice daily (BID) continuously or based on the assigned intermittent schedule within 60 minutes prior to PDR001 infusion. PDR001 400 mg was administered via IV infusion over 30 minutes once every 4 weeks. Each treatment cycle was 28 days. Patients enrolled in the Japanese safety run-in part received NIR178 as single agent for the first cycle (28 days). If the patients completed Cycle 1 without experiencing dose limiting toxicities (DLTs), they initiated combination therapy with PDR001 starting Cycle 2 onwards, and continued at the same dose of NIR178. An additional cohort in the Japanese safety run-in part of the study received NIR178 in combination with PDR001 starting with Cycle 1. If the patients complete Cycle 1 without experiencing DLTs, they continued to receive combination treatment.

Patients received 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.

Part 1, Part 3 and the Japanese safety run-in part were not randomized. In Part 2, patients were randomized to one of the 3 treatment arms in a ratio of 1:1:1.

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

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

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.

For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL).

For Cheson 2014 criteria, CR= Target nodes/nodal masses must regress to ≤1.5 cm in longest diameter (LDi), no extralymphatic sites of disease, absent non-measured lesions, organ enlargement regress to normal, no new lesions, and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative); PR= ≥50% decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes, absent or regressed non-measured lesions, spleen must have regressed by \>50% in length beyond normal, and no new lesions.

ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1.

For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).

Prostate-specific antigen (PSA) levels were assessed in serum. Rising PSA is generally a manifestation of progression of prostate cancer.

DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.

DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).

DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL).

DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.

DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.

DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.

DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.

DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per Cheson 2014 criteria for DLBCL. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1.

PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST.

PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.

PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Cheson 2014 for DLBCL.

PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.

OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan (SAP).

OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.

The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.

Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.

The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.

Number of participants with at least one dose reduction of NIR178 and number of participants with at least one dose interruption of NIR178. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.

Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. Dose reductions were not permitted for PDR001.

Dose intensity of NIR178 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days.

Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and then multiplied by 28 days.

PDR001 immunogenicity was evaluated in serum samples. Patient anti-drug antibodies (ADA) status was defined as follows:

* ADA-negative at baseline: ADA-negative sample at baseline
* ADA-positive at baseline: ADA-positive sample at baseline
* ADA-negative post-baseline: ADA-negative sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples
* Treatment-reduced ADA-positive: ADA-positive sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples
* Treatment-induced ADA-positive: ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
* Treatment-boosted ADA-positive: ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample
* ADA-inconclusive: patient who does not qualify for any of the above definitions or a patient for which the baseline sample is missing

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with NIR178 as single agent or in combination with PDR001 during the Japan safety run-in part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.

Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.

PK parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.

NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.

NJI765 is a NIR178 metabolite. Pharmacokinetic (PK) parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.

NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.

PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.

PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.

PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation.

Novartis Pharmaceuticals

Deaths in the survival period are not considered Adverse Events (AEs). No AEs were collected in the survival period.

NIR178 160 mg twice daily continuous in combination with PDR001 in patients with renal cell carcinoma (RCC) who had not been previously treated with immuno-oncology therapy. Safety data up to 150 days after last dose of NIR178+PDR001

Part 1: RCC naïve 160 mg

NIR178 240 mg twice daily continuous in combination with PDR001 in patients with renal cell carcinoma (RCC), naïve and pretreated with immuno-oncology therapy. Safety data up to 150 days after last dose of NIR178+PDR001

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Open-label, Phase II Study of AZD4635 in Patients With Prostate Cancer	NCT04089553	Prostate Cancer Metastatic Cast...	AZD4635 Oleclumab Durvalumab	18 Years - 130 Years	AstraZeneca
A Phase 2 Study of NIR178 in Combination With PDR001 in Patients With Solid Tumors and Non-Hodgkin Lymphoma	NCT03207867	NSCLC, Non Smal... RCC, Renal Cell... Pancreatic Canc... Urothelial Canc... Head and Neck C... DLBCL, Diffused... MSS, Microsatel... TNBC, Triple Ne... Melanoma mCRPC, Metastat...	NIR178 PDR001	18 Years -	Novartis
A Phase I/Ib Study of NZV930 Alone and in Combination With PDR001 and /or NIR178 in Patients With Advanced Malignancies.	NCT03549000	Non-small Cell ... Triple Negative... Pancreatic Duct... Colorectal Canc... Ovarian Cancer Renal Cell Carc... Metastatic Cast...	NZV930 PDR001 NIR178	18 Years -	Novartis
Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study	NCT03381274	Carcinoma, Non-...	Oleclumab Osimertinib AZD4635	18 Years - 101 Years	MedImmune LLC
A Phase 2 Study of NIR178 in Combination With PDR001 in Patients With Solid Tumors and Non-Hodgkin Lymphoma	NCT03207867	NSCLC, Non Smal... RCC, Renal Cell... Pancreatic Canc... Urothelial Canc... Head and Neck C... DLBCL, Diffused... MSS, Microsatel... TNBC, Triple Ne... Melanoma mCRPC, Metastat...	NIR178 PDR001	18 Years -	Novartis

Spots Global Cancer Trial Database for a2ar

Every month we try and update this database with for a2ar cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for a2ar

Every month we try and update this database with for a2ar cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for a2ar cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.