Primary outcomeNumber· 28 days
Dose Limiting Toxicities (DLTs) - Phase Ib
| Group | Value (Participants) |
|---|---|
| BYL 200mg + AMG 12mg/kg | 0 |
| BYL 300mg + AMG 12mg/kg | 0 |
| BYL 350mg + AMG 12mg/kg | 1 |
Trial · Interventional
TerminatedPhase 1/2Results postedRegistry dataA Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
This trial was stopped early.
The registry gives no reason.
Results were posted for this trial.
This trial does not test a peptide that PepBank tracks.
- Names IGF-1 (mecasermin), does not test it. It appears in the description.
Overview
- Status
- Terminated
- Phase
- Phase 1/2
- Enrollment
- 47 participants (actual)
- Sponsor
- Novartis Pharmaceuticals · Industry
- Design
- Allocation not applicable · Open label (no masking)
- Countries
4 countries
United States, Belgium, Canada, Spain
- Start
- 27 Nov 2012
- Primary completion
- 26 Dec 2014
- Completion
- 1 Jun 2017
- First posted
- 16 Oct 2012 (estimated)
- Last update posted
- 13 Sept 2018
- Conditions
- PIK3CA Mutated Advanced Solid Tumors · PIK3CA Amplified Advanced Solid Tumors
Timeline
1 trial · 1 stopped early · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2012201320142015201620172018
- Ph 1/2Terminated
A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
NCT0170816127 Nov 2012 to 1 Jun 2017
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.
Interventions
- BYL719Drug
- AMG 479Drug
Arms1
Experimental
BYL719 + AMG 479
For: Dose escalation phase/Phase II Expansion Phase. Cohorts of 3-6 patients were to be enrolled sequentially until an MTD or a recommended Phase II dose were defined. All patients were to receive the combination treatment. Sequential cohorts may receive different doses of the combination. In the Phase II expansion, all patients were to receive the same combination treatment.
Primary outcomes2
Outcomes the sponsor listed as primary.
Dose Limiting Toxicities (DLTs) - Phase Ib
Time frame · 28 days
Registry description
Phase lb only
Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
Time frame · Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
Registry description
The antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Overall response rate is defined as the proportion of patients who have a best overall response of complete response or partial response assessed per RECIST 1.1.
Secondary outcomes(9)
Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib
Time frame · Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
Registry description
The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1
Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib
Time frame · Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
Registry description
The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1
Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
Time frame · Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
Registry description
the antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter
Cmax of BYL - Phase Ib
Time frame · Cycle 1 Day 1, Cycle 1 Day 15
Registry description
Serum concentration for BYL719 (alpelisib) 1 cycle - 28 days of treatment
Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib
Time frame · Cycle 1 Day 1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)
Registry description
Area under curve for BYL719 (alpelisib) 1 cycle - 28 days of treatment
Tmax and T Half of BYL - Phase Ib
Time frame · Cycle 1 Day 1, Cycle 1 Day 15
Registry description
Tmax and half life of BYL719 (Alpelisib) 1 cycle - 28 days of treatment
Cmax of AMG - Phase Ib
Time frame · Cycle 1 Day 15
Registry description
Serum concentration for AMG 479 (ganitumab) 1 cycle - 28 days of treatment
Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib
Time frame · Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)
Registry description
Area under curve for AMG 479 (ganitumab) 1 cycle - 28 days of treatment
Tmax and T Half of AMG - Phase Ib
Time frame · Cycle 1 Day 15
Registry description
Tmax and half life of AMG 479 (ganitumab) 1 cycle - 28 days of treatment
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Primary outcomeNumber· Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
| Group | Value (Percentages of participants) |
|---|---|
| HR+BC - Phase II | 12.5 |
| Ovarian - Phase II | 16.7 |
| All Patients - Phase | 13.0 |
Secondary and other outcome results(6)
Secondary outcomeNumber· Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib
| Group | Value (Participants) |
|---|---|
| BYL 200mg + AMG 12mg/kg | 0 |
| BYL 300mg + AMG 12mg/kg | 0 |
| BYL 350mg + AMG 12mg/kg | 0 |
Secondary outcomeNumber· Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib
| Group | Value (Percentages of participants) |
|---|---|
| BYL 200mg + AMG 12mg/kg | 25.0 |
| BYL 300mg + AMG 12mg/kg | 9.1 |
| BYL 350mg + AMG 12mg/kg | 50.0 |
Secondary outcomeNumber· Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
| Group | Value (Percentages of participants) |
|---|---|
| HR+BC - Phase II | 43.8 |
| Ovarian - Phase II | 50.0 |
| All Patients - Phase II | 47.8 |
Secondary outcomeMean· Cycle 1 Day 1, Cycle 1 Day 15
Cmax of BYL - Phase Ib
| Group | Value (ng/mL) | Spread |
|---|---|---|
| BYL 200mg + AMG 12mg/kg | 2070 | 1040 |
| BYL 300mg + AMG 12mg/kg | 2620 | 1260 |
| BYL 350mg + AMG 12mg/kg | 2640 | 888 |
Secondary outcomeMean· Cycle 1 Day 1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)
Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib
| Group | Value (hr*ng/mL) | Spread |
|---|---|---|
| BYL 200mg + AMG 12mg/kg | 19900 | 8700 |
| BYL 300mg + AMG 12mg/kg | 23400 | 10500 |
| BYL 350mg + AMG 12mg/kg | 25200 | 9200 |
Secondary outcomeMedian· Cycle 1 Day 1, Cycle 1 Day 15
Tmax and T Half of BYL - Phase Ib
| Group | Value (hr) |
|---|---|
| BYL 200mg + AMG 12mg/kg | 2.78 |
| BYL 300mg + AMG 12mg/kg | 1.97 |
| BYL 350mg + AMG 12mg/kg | 2.36 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| BYL 200mg + AMG 12 mg/kgBYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors | 4 / 4 | 1 / 4 | 4 / 4 |
| BYL 300mg + AMG 12 mg/kgBYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors | 8 / 10 | 5 / 10 | 10 / 10 |
| BYL 350mg + AMG 12 mg/kgBYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors | 8 / 10 | 5 / 10 | 10 / 10 |
| HR + BC - Phase IIPatients with PIK3CA mutated or amplified hormone receptor (HR) positive breat carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg | 13 / 16 | 9 / 16 | 16 / 16 |
| Ovarian - Phase IIPatients with other than Breast and Ovarian cancer treated in the phase II | 5 / 6 | 5 / 6 | 6 / 6 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies0
Studies that cite this trial.
No study cites this trial.
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Key inclusion criteria:
* Written informed consent.
* Patients aged ≥ 18 years (male or female).
* Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue:
* Hormone receptor positive breast carcinoma
* Ovarian carcinoma
* Other tumors upon agreement with sponsor
* Adequate organ function
* Negative serum pregnancy test
Key exclusion criteria:
* Patients with known history of severe infusion reactions to monoclonal antibodies.
* Patients with primary CNS tumor or CNS tumor involvement.
* History of thromboembolic event requiring full-dose anti-coagulation therapy any time prior to enrollment.
* Clinically significant cardiac disease.
* History of another malignancy within last 2 years.
* Pregnant or nursing (lactating) women.
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