Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Carboplatin

Spartalizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Participants received LAG525 and PDR001 administered as infusion once every 3 weeks

Participants received LAG525, PDR001 and carboplatin administered as infusion once every 3 weeks.

Participants received LAG525 and carboplatin administered as infusion once every 3 weeks

LAG525 was a concentrate for solution for intravenous infusion, came in 100mg vials as a liquid formulation for infusion and was dosed at 400mg every 21 days. For all arms, LAG525 was infused first

LAG525

Spartalizumab was a concentrate for solution for intravenous infusion, came in 100mg vials as a liquid formulation for infusion and was dosed at 300mg every 21 days. Spartalizumab was infused after LAG525

PDR001

Carboplatin was a concentrate for solution for intravenous infusion, came in 100mg/mL and was dosed per area under the curve (AUC) 6 every 21 days. Carboplatin was infused once LAG525 and spartalizumab infusions were completed

Novartis Pharmaceuticals

The main purpose of this study was to assess the antitumor activity of three combinations: i) LAG525 + spartalizumab; ii) LAG525 + spartalizumab + carboplatin, and iii) LAG525 + carboplatin in participants with advanced triple-negative breast cancer (TNBC) in first or second line therapy.

This was an open-label, Phase II, randomized, multicenter study to assess the efficacy, safety, and pharmacokinetic characteristics of the following three combinations: LAG525 + spartalizumab (PDR001) (Arm 1), LAG525 + spartalizumab (PDR001) + carboplatin (Arm 2), and LAG525 + carboplatin (Arm 3) in participants with advanced triple-negative breast cancer (TNBC) which progressed after adjuvant or one prior line of systemic therapy for metastatic disease.

Participants were assigned to one of the three treatment arms in a ratio of 1:1:1. In protocol amendment 3 (released on 28-Mar-2019), enrollment to treatment Arm 1 (LAG525 + spartalizumab) was prematurely closed due to a higher discontinuation rate due to progressive disease and all subsequent enrolled patients were randomized to Arms 2 and 3 only, in a ratio of 1:1.

Study treatment continued until disease progression, unacceptable toxicity, pregnancy, investigator/participant decision, start of a new anti-neoplastic therapy, withdrawal of consent, lost to follow-up, death, or study was terminated by the sponsor. The investigator might decide to stop carboplatin after 6 cycles, even if the above criteria were not met. Participants who continued to derive clinical benefit from the treatment based on the investigator's evaluation following their completion of this trial might receive post-trial access (PTA) i.e. rollover protocol or a post-study drug supply (PSDS).

The end of study was defined as the earliest occurrence of one of the following: (1) all participants had died or (2) discontinued from the study, or (3) another clinical study became available that could continue to provide study treatment in this participant population and all ongoing participants were eligible to be transferred to that clinical study.

A Study of Efficacy and Safety of LAG525 in Combination With Spartalizumab, or With Spartalizumab and Carboplatin, or With Carboplatin, in Patients With Advanced Triple-negative Breast Cancer

A Phase II Open-label, Randomized, Three-arm, Multicenter Study of LAG525 Given in Combination With Spartalizumab (PDR001), or With Spartalizumab and Carboplatin, or With Carboplatin, as First or Second Line Therapy in Patients With Advanced Triple-negative Breast Cancer

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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com.

Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment. The 95% CIs were computed using two-sided exact binomial method.

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.

CBR is defined as the percentage of participants with a best overall response (BOR) of confirmed CR or PR, or stable disease (SD) lasting 24 weeks or longer, according to RECIST 1.1 criteria. The 95% CI were computed using two-sided exact binomial method.

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.

SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.

DOR is the time between the first documented response (CR or PR) and the first documented progression or death due to underlying cancer based on RECIST1.1 and as per investigator's assessment. The DOR distribution was estimated using the Kaplan-Meier method and the 95% confidence intervals using the method of Brookmeyer and Crowley. If progression or death did not occur, the participant was censored at the date of last adequate tumor assessment.

CR: Disappearance of all non-nodal target lesions and 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.

Progression: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. The sum must also demonstrate an absolute increase of at least 5 mm.

TTR is the time from date of randomization to first documented response of CR or PR based on investigators' assessment and according to RECIST 1.1. Median TTR was summarized using descriptive statistics.

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.

PFS is defined as time from date of randomization to the date of first documented progression or death due to any cause. PFS was assessed via investigator's assessment according to RECIST 1.1. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed prior to the analysis cut-off date or before the start of the new anticancer therapy date, whichever is earlier. The PFS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley.

OS is defined as the time from date of randomization to date of death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date). The OS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-504h was defined as the area under the plasma concentration-time curve from time zero to 504h.

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed plasma LAG525 concentration

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of LAG525

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum LAG525 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed PDR001 serum concentration

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of PDR001

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum PDR001 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as total platinum).

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as total platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as total platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as total platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as ultrafilterable platinum).

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as ultrafilterable platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as ultrafilterable platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as ultrafilterable platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment)

Number of participants who had an ADA positive result at baseline for LAG525

Number of participants who were treatment-induced ADA positive for LAG525 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for LAG525 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer)

Number of participants who had an ADA positive result at baseline for PDR001.

Number of participants who were treatment-induced ADA positive for PDR001 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for PDR001 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer)

The safety analysis was performed in the safety set including all participants who received at least one dose of study treatment (i.e., at least one dose of any component of the study treatment, including incomplete infusion of spartalizumab, LAG525 or carboplatin).

LAG525 + PDR001 (On-treatment Period)

LAG525 + PDR001 (Extended Safety Follow-up Period)

LAG525 + PDR001+Carboplatin (On-treatment Period)

LAG525 + PDR001+Carboplatin (Extended Safety Follow-up Period)

LAG525 +Carboplatin (On-treatment Period)

LAG525 +Carboplatin (Extended Safety Follow-up Period)

LAG525 + PDR001

LAG525+ PDR001+ Carboplatin

LAG525 + Carboplatin

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Study director

Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization.

Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1

FAS: All participants to whom study treatment was assigned by randomization.

Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1

Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1

Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1

Progression Free Survival (PFS)

Overall Survival (OS)

Cycle 1

Cycle 3

LAG525 pharmacokinetic analysis set (PAS-LAG525) including all participants who provided at least one evaluable LAG525 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

Pharmacokinetics (PK) Parameter, Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504h) of LAG525

PAS-LAG525 including all participants who provided at least one evaluable LAG525 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

PK Parameter, Cmax of LAG525

PK Parameter, AUClast of LAG525

PK Parameter, Tmax of LAG525

PDR001 pharmacokinetic analysis set (PAS-PDR001) including all participants who provided at least one evaluable PDR001 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

PK Parameter, AUC0-504h of PDR001

PAS-PDR001 including all participants who provided at least one evaluable PDR001 PK concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

PK Parameter, Cmax of PDR001

PK Parameter, AUClast of PDR001

PK Parameter, Tmax of PDR001

Carboplatin (plasma) PAS including all participants who provided at least one evaluable carboplatin PK plasma concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

PK Parameter, AUC0-4h of Carboplatin (Total Platinum)

PK Parameter, Cmax of Carboplatin (Total Platinum)

PK Parameter, AUClast of Carboplatin (Total Platinum)

Carboplatin (plasma) PAS including all participants who provided at least one evaluable carboplatin PK plasma concentration.Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

PK Parameter, Tmax of Carboplatin (Total Platinum)

Carboplatin (plasma ultrafiltrate) PAS including all participants who provided at least one evaluable carboplatin PK plasma ultrafiltrate concentration. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.

PK Parameter, AUC0-4h of Carboplatin (Ultrafilterable Platinum)

PK Parameter, Cmax of Carboplatin (Ultrafilterable Platinum)

PK Parameter, AUClast of Carboplatin (Ultrafilterable Platinum)

PK Parameter, Tmax of Carboplatin (Ultrafilterable Platinum)

LAG525 Immunogenicity (IG) prevalence set: all participants in the FAS wo received at least one dose of LAG525 with a determinant baseline LAG525 IG sample or at least one determinant post-baseline LAG525 IG sample.

Number of Participants With Anti-drug Antibodies (ADA) at Baseline for LAG525

LAG525 immunogenicity incidence set: all participants in the LAG525 immunogenicity prevalence set with a determinant LAG525 baseline IG sample and at least one determinant LAG525 post-baseline IG sample.

Number of Participants With Anti-drug Antibodies (ADA) on Treatment for LAG525

PDR001 Immunogenicity (IG) prevalence set: all participants in the FAS who received at least one dose of PDR001 with a determinant baseline PDR001 IG sample or at least one determinant post-baseline PDR001 IG sample

Number of Participants With Anti-drug Antibodies (ADA) at Baseline for PDR001

PDR001 Immunogenicity incidence set: all subjects in the PDR001 Immunogenicity prevalence set with a determinant PDR001 baseline IG sample and at least one determinant PDR001 post-baseline IG sample.

Number of Participants With Anti-drug Antibodies (ADA) on Treatment for PDR001

On-treatment

Extended safety follow-up deaths

Post-treatment deaths

All deaths

On-treatment deaths were collected from first dose of study medication to 30 days after the last dose of study medication for a maximum duration of 2.9 years.

Extended safety follow up deaths were collected from day 31 post treatment up to 150 days post-treatment, for a maximum duration of 3.2 years.

Post-treatment deaths were collected after 150 days post-treatment, for a maximum duration of 3.2 years.

Safety set: all participants who received at least one dose of study treatment (i.e., at least one dose of any component of the study treatment, including incomplete infusion of spartalizumab, LAG525 or carboplatin).

All Collected Deaths

Overall Study

Immunomodulating Agents

LIVI (Liquid in vial) Concentrate for Solution for infusion

spartalizumab

LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion

NIR178

capmatinib

MCS110

LIVI (Liquid in vial) Solution for injection

canakinumab

This is a Phase Ib, open label, dose escalation study of spartalizumab + LAG525 in combination with NIR178, capmatinib, MCS110, or canakinumab, followed by a dose expansion in adult patients with advanced or metastatic TNBC.

During the dose-escalation part of each treatment arm, patients will be treated with fixed doses of spartalizumab + LAG525 in combination with partner investigational drugs to be escalated until the MTD is reached or a lower RDE is established: NIR178, capmatinib, MCS110, or canakinumab. It is anticipated that other partner study drugs may be added in the future by protocol amendment.

After the determination of the MTD/RDE for a particular treatment arm, dose expansion may begin in that arm in order to further assess safety, tolerability, PK/PD, and anti-tumor activity of each combination at the MTD/RDE. Dose expansion arms may initiate only after consideration by the Investigators and Novartis of all available toxicity information, the assessment of risk to future patients from the BLRM, and the available PK, preliminary efficacy, and PD information. There is no requirement for dose-escalation treatment arms reaching an MTD/RDE to proceed to dose expansion.

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).

A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Immunotherapy Combinations in Adult Patients With Triple-negative Breast Cancer

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

Participnats randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks

Participants randomized to receive to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks

LAG-3 positive participants received LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

400 mg of PDR001 administered every 4 weeks intravenously

600 mg of LAG525 administered every 4 weeks intravenously

400 mg of INC280 administered twice daily orally

INC280

200 mg of ACZ885 administered every 4 weeks subcutaneosuly

ACZ885

600 mg of LEE011 orally taken once daily on Days 1-21 of a 28-day cycle

LEE011

The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma

This study was a randomized, open-label, two-part, multi-center, open platform phase II study designed to evaluate the efficacy and safety of the anti-PD-1 antibody PDR001 in combination with novel agents for previously treated unresectable or metastatic melanoma. Additionally, a non-randomized single-arm was added based on interim analysis findings to assess the efficacy and safety of PDR001 in combination with LAG525 in subjects with previously treated unresectable or metastatic LAG-3 positive melanoma.

The study consisted of two parts: the selection part and the expansion part, which were applicable to both the randomized and non-randomized sections. In the randomized section, participants were randomized to one of four combination arms available for enrollment:

* Arm 1: LAG525 600 mg intravenously (i.v.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
* Arm 2: INC280 400 mg orally (p.o.) twice daily (BID) and PDR001 400 mg i.v. Q4W.
* Arm 3: ACZ885 300 mg subcutaneously (s.c.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
* Arm 4: LEE011 600 mg p.o. once daily (QD) on Days 1-21 of a 28-day cycle and PDR001 400 mg i.v. Q4W.

At each interim analysis, the following determinations were made: (1) which arm met the pre-specified efficacy criteria and expanded to the expansion part, (2) which arms continued enrollment in selection part (up to 45 subjects), and (3) which arms were discontinued due to futility, considering efficacy, safety, and biomarker data. The expansion phase included enrollment of subjects only in the combination arms that met the pre-specified criteria in selection part.

In the non-randomized section, a single combination arm was opened for enrollment in selection part:

• Arm 1A: LAG525 600 mg i.v. Q4W and PDR001 400 mg i.v. Q4W, assessed in a population selected based on the LAG-3 status of their tumor.

Arm 1A would be eligible for enrollment in expansion part only if it met the pre-specified criterion for this arm.

Participants received the study treatment corresponding to their assigned arm on a 28-day cycle basis until disease progression, as determined by local assessment using RECIST v1.1 criteria, or until certain events occurred, such as unacceptable toxicity, initiation of subsequent anti-cancer therapy, withdrawal of consent, investigator's decision, loss to follow-up, death, or termination of the study by the sponsor. Following discontinuation of the study treatment, all subjects were monitored for safety evaluations for up to 150 days after their last dose of the study treatment.

After approval of protocol amendment 5 (26Jun2020), a non-randomized single arm was added

Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma

A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma

ORR defined as the percentage of patients with a best overall response of either confirmed complete response (CR) or partial response (PR) as per local review by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and assessed by computed tomography (CT)/ magnetic resonance imaging (MRI).

CR:Disappearance of all non-nodal target and non-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.

DOR defined as the time from date of first documented CR or PR to date of first documented disease progression (as per local review by RECIST v1.1 and assessed by CT/MRI) or death due to any cause. Subjects continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment.

CR:Disappearance of all non-nodal target and non-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.

OS was defined as the time from date of randomization (or date of first dose of study treatment in non-randomized part) to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method, and the medians and 95% confidence intervals of the medians were presented.

PFS was defined as the time between the date of randomization (or date of first dose of study treatment in non-randomized section) to the date of event defined as the first documented disease progression (as per local review by RECIST v1.1 and assessed by CT/MRI) or death due to any cause. If a subject had not had an event before leaving study or initiation of subsequent anticancer therapy, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using the Kaplan-Meier method, medians and 95% confidence interval of the medians were presented.

DCR was defined as the percentage of participants with best overall response of CR, PR or stable disease (SD) (as per local review by RECIST v1.1 and assessed by CT/MRI).

CR:Disappearance of all non-nodal target and non-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.

SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.

Percentage of participants who had a PDR001 ADA positive result at baseline.

Percentage of participants who had a LAG525 ADA positive result at baseline. Only applicable for participants enrolled in Arm 1 and Arm 1A.

Percentage of participants who had an ACZ885 ADA positive result at baseline. Only applicable for subjects enrolled in Arm 3.

Percentage of participants who tested positive for treatment-induced ADA for PDR001 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for PDR001 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment).

Percentage of participants who tested positive for treatment-induced ADA for LAG525 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for LAG525 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment). Only applicable for subjects enrolled in Arm 1 and Arm 1A.

Percentage of participants who tested positive for treatment-induced ADA for ACZ885 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for ACZ885 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment). Only applicable for subjects enrolled in Arm 3.

Biomarker parameters included: 1) number of tumor infiltrating T cells (TIL), 2) activation level of TIL, and 3) changes in immune response gene expression signatures. For the number of TILs, an increase in tumoral CD8+ cell numbers compared to baseline was considered favorable. The activation level of TIL was assessed by the percentage of tumoral CD8+ cells expressing GzmB (a marker for cytotoxic activity) or Ki67 (a marker for cell proliferation), where an increase in either GZMB+/CD8+ or KI67+/CD8+ post-baseline was considered favorable. Changes in immune response gene expression signatures were evaluated by the levels in T-cell inflamed signature (TIS), where an increase from baseline was considered favorable.

To be categorized as having a pFBP, a subject must meet the favorable criteria for at least two of the three biomarker parameters. The percentage of participants with pFBP was assessed.

Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered AEs. The total number at risk in the post treatment survival includes patients that entered the post treatment survival follow-up period. Safety analyses were performed in the safety set, including all participants who received at least one dose of treatment

AEs collected during on-treatment period (up to 30 days post-treatment)

Arm 1: LAG525 + PDR001 (Randomized Part)- On-treatment Period

AEs collected during extended safety follow-up period (from day 31 post-treatment up to 150 days post last dose of PDR001 \[if \>30 days post-treatment\])

Arm 1: LAG525 + PDR001 (Randomized Part)- Extended Safety Follow-up

Deaths collected in the post- treatment survival follow-up period (starting from day 151 post- treatment). No AEs were collected during this period

Arm 1: LAG525 + PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 2: INC280+PDR001 (Randomized Part)- On-treatment Period

Arm 2: INC280+PDR001 (Randomized Part) - Extended Safety Follow-up

Arm 2: INC280+PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 3: ACZ885 + PDR001 (Randomized Part)- On-treatment Period

Arm 3: ACZ885 + PDR001 (Randomized Part)- Extended Safety Follow-up

Arm 3: ACZ885 + PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 4: LEE011 + PDR001 (Randomized Part)- On-treatment Period

Arm 4: LEE011 + PDR001 (Randomized Part)- Extended Safety Follow-up

Arm 4: LEE011 + PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 1A: LAG525 + PDR001 (Non-randomized Part)- On-treatment Period

Arm 1A: LAG525 + PDR001 (Non-randomized Part)- Extended Safety Follow-up

Arm 1A: LAG525 + PDR001 (Non-randomized Part)- Post-treatment Survival Follow-up

Participants randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Arm 1: LAG525 + PDR001 (Randomized Section)

Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Arm 2: INC280+PDR001 (Randomized Section)

Participants randomized to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Arm 3: ACZ885 + PDR001 (Randomized Section)

Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Efficacy and Safety of LAG525 in Combination With Spartalizumab, or With Spartalizumab and Carboplatin, or With Carboplatin, in Patients With Advanced Triple-negative Breast Cancer	NCT03499899	Triple-negative...	LAG525 PDR001 Carboplatin	18 Years -	Novartis
Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).	NCT03742349	Triple Negative...	spartalizumab LAG525 NIR178 capmatinib MCS110 canakinumab	18 Years -	Novartis
Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma	NCT03484923	Melanoma	PDR001 LAG525 INC280 ACZ885 LEE011	18 Years -	Novartis
A Study of Efficacy and Safety of LAG525 in Combination With Spartalizumab, or With Spartalizumab and Carboplatin, or With Carboplatin, in Patients With Advanced Triple-negative Breast Cancer	NCT03499899	Triple-negative...	LAG525 PDR001 Carboplatin	18 Years -	Novartis
Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma	NCT03484923	Melanoma	PDR001 LAG525 INC280 ACZ885 LEE011	18 Years -	Novartis
Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC).	NCT03742349	Triple Negative...	spartalizumab LAG525 NIR178 capmatinib MCS110 canakinumab	18 Years -	Novartis

Spots Global Cancer Trial Database for lag525

Every month we try and update this database with for lag525 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 lag525

Every month we try and update this database with for lag525 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 lag525 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.