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To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician's choice in previously treated esophageal squamous cell carcinoma patients.
The study design included a Phase 1b dose escalation portion to define the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) for the combination of LJM716 and alpelisib, followed by an open-label, randomized Phase 2 part to compare anti-tumor activity of LJM716-alpelisib combination versus physician's choice of second-line therapy (paclitaxel, docetaxel, irinotecan). However, the phase 2 part was not conducted as the study was terminated early due to limited anti-tumor activity with LJM716-alpelisib combination observed in phase 1b.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LJM716-BYL719 arm | Experimental | approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the LJM716-BYL719 combination arm to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan). |
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| Paclitaxel, Docetaxel or Irinotecan arm | Active Comparator | approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the Paclitaxel, Docetaxel or Irinotecan arm (physician's choice arm) to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the LJM716-BYL719 combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LJM716 | Drug | LJM716 (10-40 mg/kg) will be given as a once weekly infusion beginning on cycle 1 day 1. The doses of LJM716 will be increased as dose escalation proceeds until a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) is established. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase Ib primary outcome measure: Incidence rate of dose limiting toxicities (DLTs). | The open-label dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or Recommended Phase II Dose (s) guided by the safety (incidence of dose limiting toxicities), efficacy, pharmacokinetics and pharmacodynamics data. | approximately 8 months |
| Phase II primary outcome measure: Progression free survival (PFS) | Progression-free survival is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate assessment. | Every 6 weeks from the date of the baseline computed-tomography (CT) scan until the date of first documented evidence of disease progression or date of death, whichever comes first, assessed up to 24 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of the LJM716-BYL719 | This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity. | Every 21 days from the date of the baseline visit until the end of study visit (about 5 months) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Medical Center Dept of Onc | Chicago | Illinois | 60637 | United States | ||
| Karmanos Cancer Institute Dept of Onc |
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| Label | URL |
|---|---|
| Results for CLJM716X2103 from the Novartis Clinical Trials website | View source |
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| BYL719 | Drug | BYL719 (200-400 mg) will be administered orally on a once daily schedule starting cycle 1 day 1. The doses of BYL719 will be increased as dose escalation proceeds until a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) is established. |
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| Paclitaxel | Drug | In the Phase II portion of the study Paclitaxel is one of the 3 physician's choice drug which allows single-agent paclitaxel to be used per manufacturer's label. |
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| Docetaxel | Drug | In the Phase II portion of the study Docetaxel is one of the 3 physician's choice drug which allows single-agent docetaxel to be used per manufacturer's label. |
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| Irinotecan | Drug | In the Phase II portion of the study Irinotecan is one of the 3 physician's choice drug which allows single-agent irinotecan to be used per manufacturer's label |
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| Best overall response (BOR), per RECIST 1.1 (Ph 1b ) | BOR will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan. | Every 21 days from the date of baseline computed tomography (CT) scan until end of treatment visit (about 4 months) |
| Plasma concentration versus time profiles Plasma PK parameters of LJM716, BYL719 | Plasma concentration versus time profiles Plasma PK parameters will be used to characterize the PK profiles of LJM716 and BYL719 when used in combination | Baseline, 2hr,4hr,8hr,24hr,48hr,96hr, 168 hr, every 21 days for 10 cycles (21 days each) and at end of treatment (about 4 months) |
| Overall response rate (ORR) per RECIST 1.1 (Ph 1b ) | Overall response rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan. | Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months) |
| Duration of response (DOR) per RECIST 1.1 (Ph 1b ) | Duration of response will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan. | Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months) |
| Disease control rate (DCR) per RECIST 1.1 (Ph 1b ) | Disease control rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan. | Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months) |
| Overall survival (OS) per RECIST 1.1 (for Ph 1b ) | Overall survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan. | Every 21 days from the date of the baseline computed tomography (CT) scan until the end of treatment visit (about 4 months) |
| Progression free survival (PFS) per RECIST 1.1 (Ph 1b ) | Progression free survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan. | Every 21 days from the date of the baseline computed tomography (CT) scan until the end of study visit (about 5 months) |
| Detroit |
| Michigan |
| 48201 |
| United States |
| University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology | Houston | Texas | 77030-4009 | United States |
| Novartis Investigative Site | Brussels | 1200 | Belgium |
| Novartis Investigative Site | Toronto | Ontario | M5G 2M9 | Canada |
| Novartis Investigative Site | Hong Kong | Hong Kong |
| Novartis Investigative Site | Singapore | 169610 | Singapore |
| Novartis Investigative Site | Seoul | Korea | 03080 | South Korea |
| Novartis Investigative Site | Seoul | Korea | 05505 | South Korea |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | Tainan | Taiwan ROC | 70421 | Taiwan |
| Novartis Investigative Site | Taipei | 10048 | Taiwan |
| Novartis Investigative Site | Manchester | M20 2BX | United Kingdom |
| ID | Term |
|---|---|
| D000077277 | Esophageal Squamous Cell Carcinoma |
| D004938 | Esophageal Neoplasms |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018307 | Neoplasms, Squamous Cell |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| C000619694 | elgemtumab |
| C585539 | Alpelisib |
| D017239 | Paclitaxel |
| D000077143 | Docetaxel |
| D000077146 | Irinotecan |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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