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
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LAG525 + spartalizumab Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks |
Drug: LAG525
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
Drug: Spartalizumab
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
Other Names:
|
| Experimental: LAG525+spartalizumab+carboplatin Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. |
Drug: LAG525
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
Drug: Spartalizumab
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
Other Names:
Drug: Carboplatin
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
|
| Experimental: LAG525 + carboplatin Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
Drug: LAG525
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
Drug: Carboplatin
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
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1 [Up to approximately 14 months]
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.
Secondary Outcome Measures
- Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1 [Up to approximately 14 months]
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.
- Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1 [From first documented response up to disease progression or death due to underlying cancer, whichever occurs first, up to approximately 14 months]
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.
- Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1 [From date of randomization to first documented response (CR or PR), up to approximately 14 months]
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.
- Progression Free Survival (PFS) [From date of randomization to disease progression or death due to any cause, whichever occurs first, up to approximately 14 months]
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.
- Overall Survival (OS) [From date of randomization to date of death due to any cause, up to 18 months]
OS is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, then OS will be 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
- Pharmacokinetics (PK) Parameter, LAG525 Serum Concentrations [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
LAG525 serum concentrations will be presented at scheduled time points
- PK Parameter, Spartalizumab Serum Concentrations [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
Spartalizumab serum concentrations will be presented at scheduled time points
- PK Parameter, Carboplatin Plasma Concentrations [Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days]
Carboplatin plasma concentrations will be presented at scheduled time points
- PK Parameter, Cmax of LAG525 [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
The maximum observed plasma LAG525 concentration
- PK Parameter, Cmax of Spartalizumab [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
The maximum observed spartalizumab serum concentration
- PK Parameter, Cmax of Carboplatin [Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days]
The maximum observed carboplatin plasma concentration
- PK Parameter, AUClast of LAG525 [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of LAG525
- PK Parameter, AUClast of Spartalizumab [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of spartalizumab
- PK Parameter, AUClast of Carboplatin [Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days]
The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin
- PK Parameter, Tmax of LAG525 [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
The time to reach maximum LAG525 serum concentration
- PK Parameter, Tmax of Spartalizumab [Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days]
The time to reach maximum spartalizumab serum concentration
- PK Parameter, Tmax of Carboplatin [Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days]
The time to reach maximum carboplatin plasma concentration
- Anti-drug Antibodies (ADA) Prevalence at Baseline for LAG525 [Baseline]
ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline for LAG525
- Anti-drug Antibodies (ADA) Prevalence at Baseline for Spartalizumab [Baseline]
ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline for spartalizumab.
- Anti-drug Antibodies (ADA) Incidence on Treatment for LAG525 [From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years]
ADA incidence on treatment for LAG525 will be calculated as the percentage of participants who are 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 is at least the fold titer change greater than the ADA-positive baseline titer)
- Anti-drug Antibodies (ADA) Incidence on Treatment for Spartalizumab [From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years]
ADA incidence on treatment for spartalizumab will be calculated as the percentage of participants who are treatment-induced ADA positive for spartalizumab (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for spartalizumab (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Had advanced (loco-regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
-
Had measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other loco-regional therapy was to be considered measurable if disease progression at the treated site after completion of therapy is clearly documented)
-
Progressed after adjuvant or 1 prior systemic treatment in the metastatic setting. Patients with de novo metastatic disease were eligible if they received 1 prior line of therapy
-
Had received prior systemic treatment that included taxane-based chemotherapy for adjuvant or metastatic disease
-
Had a site of disease amenable to biopsy, and was willing to undergo a new tumor biopsy at screening and during therapy on this study, the latter if medically feasible. Patients with an available archival tumor tissue did not need to perform a tumor biopsy at screening if patient had not received anti-cancer therapy since the biopsy was taken.
-
PHad histologically and/or cytologically confirmed diagnosis of advanced TNBC (based on most recently analyzed biopsy from locally recurrent or metastatic site, local lab) meeting the following criteria: HER2 negative in situ hybridization test or an IHC status of 0 or 1+, and ER and PR expression was <1 percent as determined by immunohistochemistry (IHC)
Exclusion Criteria:
-
Had received prior immune checkpoint inhibitors as anticancer treatment such as anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody (any line of therapy).
-
Received prior neoadjuvant or adjuvant therapy with a platinum agent or mitomycin and experienced recurrence within 12 months after the end of the platinum-based or mitomycin containing therapy or received Platinum or mitomycin for metastatic disease
-
Had major surgery within 14 days prior to starting study treatment or had not recovered to grade 1 or less from major side effects.
-
Presence of CTCAE grade 2 toxicity or higher due to prior cancer therapy. Exception to this criterion; patients with any grade of alopecia were allowed to enter the study.
-
Had received radiotherapy ≤ 4 weeks prior to randomization (≤ 2 weeks for limited field radiation for palliation), and had not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia).
-
Had a known hypersensitivity to other monoclonal antibodies, platinum-containing compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin.
-
Had symptomatic central nervous system (CNS) metastases or CNS metastases that required local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the 2 weeks prior to first dose of study treatment. Patients with treated brain metastases would be neurologically stable and without CNS progression for at least 12 weeks prior to randomization and had discontinued corticosteroid treatment (with the exception of < 10 mg/day of prednisone or equivalent for an indication other than CNS metastases) for at least 4 weeks before first dose of any study treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ironwood Cancer and Research Centers | Chandler | Arizona | United States | 85224 |
| 2 | Highlands Oncology Group | Fayetteville | Arkansas | United States | 72703 |
| 3 | Novartis Investigative Site | Caba | Buenos Aires | Argentina | C1280AEB |
| 4 | Novartis Investigative Site | Wooloongabba | Queensland | Australia | 4102 |
| 5 | Novartis Investigative Site | Melbourne | Victoria | Australia | 3000 |
| 6 | Novartis Investigative Site | Nedlands | Western Australia | Australia | 6009 |
| 7 | Novartis Investigative Site | Liege | Belgium | 4000 | |
| 8 | Novartis Investigative Site | Montreal | Quebec | Canada | H3T 1E2 |
| 9 | Novartis Investigative Site | Quebec | Canada | G1S 4L8 | |
| 10 | Novartis Investigative Site | Paris | France | 75231 | |
| 11 | Novartis Investigative Site | Luebeck | Schleswig-holstein | Germany | 23563 |
| 12 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 13 | Novartis Investigative Site | Tübingen | Germany | 72076 | |
| 14 | Novartis Investigative Site | Budapest | Hungary | H 1122 | |
| 15 | Novartis Investigative Site | Szeged | Hungary | H-6720 | |
| 16 | Novartis Investigative Site | Tel Aviv | Israel | 6423906 | |
| 17 | Novartis Investigative Site | Napoli | Italy | 80131 | |
| 18 | Novartis Investigative Site | Nagoya-city | Aichi | Japan | 467-8602 |
| 19 | Novartis Investigative Site | Nagoya | Aichi | Japan | 466 8560 |
| 20 | Novartis Investigative Site | Yokohama-city | Kanagawa | Japan | 241-8515 |
| 21 | Novartis Investigative Site | Minato ku | Tokyo | Japan | 105-8470 |
| 22 | Novartis Investigative Site | Seoul | Korea | Korea, Republic of | 05505 |
| 23 | Novartis Investigative Site | Seoul | Korea, Republic of | 03080 | |
| 24 | Novartis Investigative Site | Ashrafieh | Lebanon | 166830 | |
| 25 | Novartis Investigative Site | El Metn | Lebanon | ||
| 26 | Novartis Investigative Site | Saida | Lebanon | 652 | |
| 27 | Novartis Investigative Site | Singapore | Singapore | 169610 | |
| 28 | Novartis Investigative Site | Sevilla | Andalucia | Spain | 41013 |
| 29 | Novartis Investigative Site | Madrid | Spain | 28034 | |
| 30 | Novartis Investigative Site | Taipei | Taiwan | 10002 | |
| 31 | Novartis Investigative Site | Taipei | Taiwan | 11217 | |
| 32 | Novartis Investigative Site | Taipei | Taiwan | ||
| 33 | Novartis Investigative Site | Songkla | Thailand | 90110 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.- CLAG525B2101
- 2017-004865-28
Study Results
Participant Flow
| Recruitment Details | The study was conducted across 33 centers in 17 countries. |
|---|---|
| Pre-assignment Detail | A total of 132 participants were screened of which 88 participants were enrolled in the study and 87 participants received at least one dose of study treatment (1 participant was not treated due to physician decision) |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin |
|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
| Period Title: Overall Study | |||
| STARTED | 20 | 34 | 34 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 20 | 34 | 34 |
Baseline Characteristics
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks | Total of all reporting groups |
| Overall Participants | 20 | 34 | 34 | 88 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
53.8
(10.22)
|
50.9
(10.88)
|
53.3
(10.78)
|
52.5
(10.65)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
20
100%
|
34
100%
|
34
100%
|
88
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Asian |
8
40%
|
8
23.5%
|
7
20.6%
|
23
26.1%
|
| Black or African American |
0
0%
|
0
0%
|
1
2.9%
|
1
1.1%
|
| Missing |
0
0%
|
3
8.8%
|
1
2.9%
|
4
4.5%
|
| White |
12
60%
|
23
67.6%
|
25
73.5%
|
60
68.2%
|
Outcome Measures
| Title | Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1 |
|---|---|
| Description | 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. |
| Time Frame | Up to approximately 14 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): All participants to whom study treatment was assigned by randomization. |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin |
|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
| Measure Participants | 20 | 34 | 34 |
| Number (95% Confidence Interval) [Percentage of participants] |
5.0
25%
|
32.4
95.3%
|
17.6
51.8%
|
| Title | Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1 |
|---|---|
| Description | 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. |
| Time Frame | Up to approximately 14 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: All participants to whom study treatment was assigned by randomization. |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin |
|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
| Measure Participants | 20 | 34 | 34 |
| Number (95% Confidence Interval) [Percentage of Participants] |
5.0
25%
|
35.3
103.8%
|
20.6
60.6%
|
| Title | Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1 |
|---|---|
| Description | 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. |
| Time Frame | From first documented response up to disease progression or death due to underlying cancer, whichever occurs first, up to approximately 14 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a confirmed CR or PR |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin |
|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
| Measure Participants | 1 | 11 | 6 |
| Median (95% Confidence Interval) [Months] |
4.9
|
13.6
|
12.6
|
| Title | Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1 |
|---|---|
| Description | 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. |
| Time Frame | From date of randomization to first documented response (CR or PR), up to approximately 14 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a confirmed CR or PR |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin |
|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
| Measure Participants | 1 | 11 | 6 |
| Median (Full Range) [Months] |
1.5
|
1.7
|
1.4
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | 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. |
| Time Frame | From date of randomization to disease progression or death due to any cause, whichever occurs first, up to approximately 14 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: All participants to whom study treatment was assigned by randomization. |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin |
|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
| Measure Participants | 20 | 34 | 34 |
| Median (95% Confidence Interval) [Months] |
1.4
|
4.3
|
3.0
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, then OS will be 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 |
| Time Frame | From date of randomization to date of death due to any cause, up to 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Pharmacokinetics (PK) Parameter, LAG525 Serum Concentrations |
|---|---|
| Description | LAG525 serum concentrations will be presented at scheduled time points |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Spartalizumab Serum Concentrations |
|---|---|
| Description | Spartalizumab serum concentrations will be presented at scheduled time points |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Carboplatin Plasma Concentrations |
|---|---|
| Description | Carboplatin plasma concentrations will be presented at scheduled time points |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Cmax of LAG525 |
|---|---|
| Description | The maximum observed plasma LAG525 concentration |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Cmax of Spartalizumab |
|---|---|
| Description | The maximum observed spartalizumab serum concentration |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Cmax of Carboplatin |
|---|---|
| Description | The maximum observed carboplatin plasma concentration |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, AUClast of LAG525 |
|---|---|
| Description | The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of LAG525 |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, AUClast of Spartalizumab |
|---|---|
| Description | The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of spartalizumab |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, AUClast of Carboplatin |
|---|---|
| Description | The area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Tmax of LAG525 |
|---|---|
| Description | The time to reach maximum LAG525 serum concentration |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Tmax of Spartalizumab |
|---|---|
| Description | The time to reach maximum spartalizumab serum concentration |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion and 1 hour (h) post-infusion), C1D8, C1D15, C2D1 (pre-infusion), C2D8, C3D1 (pre-infusion and 1h post-infusion), C3D8, C3D15, D1 of C4, C5, C6 and C7, and end of treatment, up to 2.8 years . Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PK Parameter, Tmax of Carboplatin |
|---|---|
| Description | The time to reach maximum carboplatin plasma concentration |
| Time Frame | Cycle (C) 1 Day (D) 1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion), C3D1 (pre-infusion, end of infusion, 1, 2 and 3 hours post-infusion) and C4D1 (pre-infusion). Each cycle is 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Anti-drug Antibodies (ADA) Prevalence at Baseline for LAG525 |
|---|---|
| Description | ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline for LAG525 |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin | LAG525 + Carboplatin |
|---|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks |
| Measure Participants | 17 | 32 | 32 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Anti-drug Antibodies (ADA) Prevalence at Baseline for Spartalizumab |
|---|---|
| Description | ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline for spartalizumab. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Spartalizumab Immunogenicity (IG) prevalence set: all participants in the FAS who received at least one dose of spartalizumab with a determinant baseline spartalizumab IG sample or at least one determinant post-baseline spartalizumab IG sample |
| Arm/Group Title | LAG525 + Spartalizumab | LAG525+ Spartalizumab+ Carboplatin |
|---|---|---|
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. |
| Measure Participants | 11 | 9 |
| Count of Participants [Participants] |
1
5%
|
0
0%
|
| Title | Anti-drug Antibodies (ADA) Incidence on Treatment for LAG525 |
|---|---|
| Description | ADA incidence on treatment for LAG525 will be calculated as the percentage of participants who are 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 is at least the fold titer change greater than the ADA-positive baseline titer) |
| Time Frame | From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Anti-drug Antibodies (ADA) Incidence on Treatment for Spartalizumab |
|---|---|
| Description | ADA incidence on treatment for spartalizumab will be calculated as the percentage of participants who are treatment-induced ADA positive for spartalizumab (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for spartalizumab (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer) |
| Time Frame | From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | From first dose of study treatment until last dose of study treatment plus 30 days, up to approximately 2.8 years | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Any sign or symptom that occurs during the study treatment plus 30 days post treatment. 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). | |||||
| Arm/Group Title | LAG525 + Spartalizumab | LAG525 + Spartalizumab +Carboplatin | LAG525 + Carboplatin | |||
| Arm/Group Description | Participants received LAG525 and spartalizumab administered as infusion once every 3 weeks | Participants received LAG525, spartalizumab and carboplatin administered as infusion once every 3 weeks. | Participants received LAG525 and carboplatin administered as infusion once every 3 weeks | |||
All Cause Mortality |
||||||
| LAG525 + Spartalizumab | LAG525 + Spartalizumab +Carboplatin | LAG525 + Carboplatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/19 (0%) | 2/34 (5.9%) | 1/34 (2.9%) | |||
Serious Adverse Events |
||||||
| LAG525 + Spartalizumab | LAG525 + Spartalizumab +Carboplatin | LAG525 + Carboplatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/19 (31.6%) | 12/34 (35.3%) | 14/34 (41.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/19 (0%) | 0/34 (0%) | 2/34 (5.9%) | |||
| Febrile neutropenia | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Cardiac disorders | ||||||
| Myocardial infarction | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Myocarditis | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Pericardial effusion | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Wolff-Parkinson-White syndrome | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Congenital, familial and genetic disorders | ||||||
| Fanconi syndrome | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Erosive duodenitis | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Faeces discoloured | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Intestinal ischaemia | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Nausea | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Vomiting | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| General disorders | ||||||
| Disease progression | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| General physical health deterioration | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Pain | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Hepatobiliary disorders | ||||||
| Biliary colic | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Infections and infestations | ||||||
| Pneumocystis jirovecii pneumonia | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Pneumonia | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Sepsis | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Septic shock | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Skin infection | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Subcutaneous abscess | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Thoracic vertebral fracture | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Investigations | ||||||
| Platelet count decreased | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Troponin increased | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypercalcaemia | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Metastases to meninges | 0/19 (0%) | 1/34 (2.9%) | 1/34 (2.9%) | |||
| Nervous system disorders | ||||||
| Brain oedema | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Headache | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Psychiatric disorders | ||||||
| Confusional state | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Renal and urinary disorders | ||||||
| Renal tubular acidosis | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 1/19 (5.3%) | 2/34 (5.9%) | 3/34 (8.8%) | |||
| Dyspnoea exertional | 0/19 (0%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Pleural effusion | 0/19 (0%) | 1/34 (2.9%) | 2/34 (5.9%) | |||
| Pleuritic pain | 0/19 (0%) | 0/34 (0%) | 1/34 (2.9%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| LAG525 + Spartalizumab | LAG525 + Spartalizumab +Carboplatin | LAG525 + Carboplatin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/19 (89.5%) | 34/34 (100%) | 33/34 (97.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/19 (5.3%) | 20/34 (58.8%) | 19/34 (55.9%) | |||
| Leukopenia | 0/19 (0%) | 3/34 (8.8%) | 5/34 (14.7%) | |||
| Neutropenia | 0/19 (0%) | 9/34 (26.5%) | 7/34 (20.6%) | |||
| Thrombocytopenia | 0/19 (0%) | 15/34 (44.1%) | 14/34 (41.2%) | |||
| Endocrine disorders | ||||||
| Goitre | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Hypothyroidism | 0/19 (0%) | 5/34 (14.7%) | 1/34 (2.9%) | |||
| Thyroiditis | 1/19 (5.3%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Eye disorders | ||||||
| Dry eye | 1/19 (5.3%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal distension | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Abdominal pain | 1/19 (5.3%) | 5/34 (14.7%) | 2/34 (5.9%) | |||
| Abdominal pain upper | 1/19 (5.3%) | 5/34 (14.7%) | 3/34 (8.8%) | |||
| Constipation | 3/19 (15.8%) | 7/34 (20.6%) | 16/34 (47.1%) | |||
| Diarrhoea | 0/19 (0%) | 5/34 (14.7%) | 7/34 (20.6%) | |||
| Dry mouth | 0/19 (0%) | 5/34 (14.7%) | 0/34 (0%) | |||
| Dyspepsia | 1/19 (5.3%) | 2/34 (5.9%) | 3/34 (8.8%) | |||
| Dysphagia | 0/19 (0%) | 1/34 (2.9%) | 2/34 (5.9%) | |||
| Gastrooesophageal reflux disease | 0/19 (0%) | 3/34 (8.8%) | 1/34 (2.9%) | |||
| Nausea | 3/19 (15.8%) | 18/34 (52.9%) | 13/34 (38.2%) | |||
| Toothache | 1/19 (5.3%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Vomiting | 0/19 (0%) | 7/34 (20.6%) | 7/34 (20.6%) | |||
| General disorders | ||||||
| Asthenia | 0/19 (0%) | 11/34 (32.4%) | 5/34 (14.7%) | |||
| Chest pain | 0/19 (0%) | 2/34 (5.9%) | 2/34 (5.9%) | |||
| Chills | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Fatigue | 2/19 (10.5%) | 11/34 (32.4%) | 12/34 (35.3%) | |||
| Gait disturbance | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Induration | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Influenza like illness | 1/19 (5.3%) | 2/34 (5.9%) | 2/34 (5.9%) | |||
| Malaise | 1/19 (5.3%) | 3/34 (8.8%) | 0/34 (0%) | |||
| Non-cardiac chest pain | 1/19 (5.3%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Oedema peripheral | 0/19 (0%) | 0/34 (0%) | 2/34 (5.9%) | |||
| Pain | 2/19 (10.5%) | 0/34 (0%) | 2/34 (5.9%) | |||
| Pyrexia | 1/19 (5.3%) | 4/34 (11.8%) | 3/34 (8.8%) | |||
| Infections and infestations | ||||||
| Conjunctivitis | 1/19 (5.3%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Herpes zoster | 1/19 (5.3%) | 1/34 (2.9%) | 1/34 (2.9%) | |||
| Lymphangitis | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Nasopharyngitis | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Rhinitis | 1/19 (5.3%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Skin infection | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Upper respiratory tract infection | 0/19 (0%) | 2/34 (5.9%) | 1/34 (2.9%) | |||
| Urinary tract infection | 1/19 (5.3%) | 1/34 (2.9%) | 2/34 (5.9%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 0/19 (0%) | 2/34 (5.9%) | 1/34 (2.9%) | |||
| Fall | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 1/19 (5.3%) | 6/34 (17.6%) | 1/34 (2.9%) | |||
| Aspartate aminotransferase increased | 2/19 (10.5%) | 4/34 (11.8%) | 2/34 (5.9%) | |||
| Blood alkaline phosphatase increased | 0/19 (0%) | 4/34 (11.8%) | 1/34 (2.9%) | |||
| Blood creatine phosphokinase increased | 0/19 (0%) | 0/34 (0%) | 2/34 (5.9%) | |||
| Blood thyroid stimulating hormone increased | 1/19 (5.3%) | 1/34 (2.9%) | 1/34 (2.9%) | |||
| Gamma-glutamyltransferase increased | 1/19 (5.3%) | 4/34 (11.8%) | 1/34 (2.9%) | |||
| Neutrophil count decreased | 0/19 (0%) | 11/34 (32.4%) | 6/34 (17.6%) | |||
| Platelet count decreased | 1/19 (5.3%) | 14/34 (41.2%) | 9/34 (26.5%) | |||
| SARS-CoV-2 test negative | 0/19 (0%) | 2/34 (5.9%) | 1/34 (2.9%) | |||
| Weight decreased | 0/19 (0%) | 0/34 (0%) | 2/34 (5.9%) | |||
| White blood cell count decreased | 0/19 (0%) | 5/34 (14.7%) | 1/34 (2.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 2/19 (10.5%) | 4/34 (11.8%) | 4/34 (11.8%) | |||
| Hyperglycaemia | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Hypocalcaemia | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Hypokalaemia | 0/19 (0%) | 4/34 (11.8%) | 2/34 (5.9%) | |||
| Hypomagnesaemia | 0/19 (0%) | 4/34 (11.8%) | 3/34 (8.8%) | |||
| Hyponatraemia | 1/19 (5.3%) | 1/34 (2.9%) | 1/34 (2.9%) | |||
| Hypophagia | 1/19 (5.3%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/19 (5.3%) | 3/34 (8.8%) | 4/34 (11.8%) | |||
| Back pain | 1/19 (5.3%) | 7/34 (20.6%) | 3/34 (8.8%) | |||
| Bone pain | 1/19 (5.3%) | 1/34 (2.9%) | 1/34 (2.9%) | |||
| Musculoskeletal chest pain | 0/19 (0%) | 2/34 (5.9%) | 1/34 (2.9%) | |||
| Musculoskeletal pain | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Myalgia | 2/19 (10.5%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Neck pain | 0/19 (0%) | 0/34 (0%) | 2/34 (5.9%) | |||
| Pain in extremity | 0/19 (0%) | 5/34 (14.7%) | 2/34 (5.9%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Metastases to skin | 2/19 (10.5%) | 0/34 (0%) | 0/34 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 0/19 (0%) | 1/34 (2.9%) | 6/34 (17.6%) | |||
| Dysgeusia | 1/19 (5.3%) | 2/34 (5.9%) | 1/34 (2.9%) | |||
| Headache | 2/19 (10.5%) | 8/34 (23.5%) | 4/34 (11.8%) | |||
| Intercostal neuralgia | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Paraesthesia | 1/19 (5.3%) | 0/34 (0%) | 1/34 (2.9%) | |||
| Peripheral sensory neuropathy | 0/19 (0%) | 1/34 (2.9%) | 3/34 (8.8%) | |||
| Somnolence | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 1/19 (5.3%) | 1/34 (2.9%) | 0/34 (0%) | |||
| Insomnia | 0/19 (0%) | 1/34 (2.9%) | 6/34 (17.6%) | |||
| Renal and urinary disorders | ||||||
| Polyuria | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Breast pain | 0/19 (0%) | 0/34 (0%) | 2/34 (5.9%) | |||
| Pelvic pain | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Vaginal discharge | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 2/19 (10.5%) | 7/34 (20.6%) | 4/34 (11.8%) | |||
| Dyspnoea | 1/19 (5.3%) | 4/34 (11.8%) | 6/34 (17.6%) | |||
| Haemoptysis | 0/19 (0%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Oropharyngeal pain | 0/19 (0%) | 4/34 (11.8%) | 1/34 (2.9%) | |||
| Pleural effusion | 0/19 (0%) | 1/34 (2.9%) | 3/34 (8.8%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/19 (0%) | 3/34 (8.8%) | 3/34 (8.8%) | |||
| Dry skin | 3/19 (15.8%) | 3/34 (8.8%) | 0/34 (0%) | |||
| Eczema | 1/19 (5.3%) | 2/34 (5.9%) | 0/34 (0%) | |||
| Pruritus | 2/19 (10.5%) | 4/34 (11.8%) | 1/34 (2.9%) | |||
| Rash | 2/19 (10.5%) | 6/34 (17.6%) | 1/34 (2.9%) | |||
| Skin lesion | 1/19 (5.3%) | 0/34 (0%) | 0/34 (0%) | |||
| Vascular disorders | ||||||
| Hot flush | 1/19 (5.3%) | 2/34 (5.9%) | 1/34 (2.9%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
- CLAG525B2101
- 2017-004865-28