Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
BYL719, PI3K inhibitor, PIK3CA, cetuximab, EGFR, HNSCC, RM HNSCC, platinum-based chemotherapy, (RM HNSCC) patients, resistant or ineligible/intolerant to platinum-based chemotherapy, swallowing dysfunction, G-tube, alpelisib
Brief summary
This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) patients considered to be resistant, ineligible or intolerant to platinum-based chemotherapy. The Phase Ib included three arms. Three different methods of administration and two different BYL719 formulations were studied to determine the MTD and/or RP2D of BYL719 in combination with cetuximab: Arm A - film-coated whole tablets were orally administered to patients who were able to swallow the tablets; Arm B - a drinkable suspension prepared from crushed film-coated tablets was administered orally to patients with swallowing dysfunction Arm C - a suspension from a dispersible tablet administered via G-tube, in patients with swallowing dysfunction. Arm C was used to investigate the pharmacokinetics (PK), compared to Arm A (film coated tablet), and safety of the dispersible tablet of the dispersible tablet formulation of BYL719. The Phase II investigated the clinical efficacy of BYL719 and consisted of an open label, randomized Phase II part investigating BYL719 in combination with cetuximab compared to cetuximab alone in patients resistant or intolerant to platinum and naïve to cetuximab (Scheme 1: Arm 1 and Arm 2), and a non-randomized Phase II part Scheme 2: Arm 3. In addition, patients who experienced disease progression in Arm 2 (cetuximab) were allowed to switch to the combination regimen (cross-over, Arm 2B). The safety of the BYL719 in combination with cetuximab was also further characterized in Arms 1, 2B and 3. Patients were treated until progression of disease), unacceptable toxicity, or withdrawal of informed consent, whichever occurred first (except for phase II Arm 2 had the opportunity to crossover to the combination treatment (Arm 2B). In the follow-up period all patients had to complete the safety follow-up assessments within 30 days after the last dose of the study treatment. Patients who did not have disease progression at the time of discontinuation of study treatment were radiologically followed for disease status until disease progression, initiation of subsequent anticancer therapies, or death, whichever occurred first. In addition, all patients enrolled in Phase II were followed for survival.
Interventions
DRUGBYL719 as film-coated (FC) whole tablets
Oral alpha-specific PI3K inhibitor
DRUGBYL719 as dispersible tablets (DT)
New formulation of the oral alpha-specific PI3K inhibitor
BIOLOGICALcetuximab
Recombinant chimeric monoclonal antibody driven against EGFR
DRUGBYL719 drink suspension
Oral alpha-specific PI3K inhibitor
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Patients with histologically/cytologically-confirmed HNSCC * Patients must be resistant to platinum-based chemotherapy, or be ineligible (due to medical comorbidities) or intolerant to platinum-based therapy per medical history * For Phase Ib, there is no restriction on the number of prior therapies for recurrent or metastatic disease * For Phase II, patients may have received a maximum of 1 prior line of therapy for recurrent or metastatic disease * For Phase Ib, prior cetuximab or other EGFR-targeted antibody therapy is allowed regardless of the prior treatment settings. * For Phase II, Arms 1 and 2, prior cetuximab or other EGFR-targeted antibody therapy is allowed only if administered in the induction setting, or concurrently with radiation in the curative setting, with the last dose of cetuximab administered at least 12 months prior to starting the study treatment. For Arm 3, prior cetuximab must have been administered in the curative, recurrent or metastatic disease setting and disease progression documented within 9 months of the last dose of cetuximab administered in that setting. This regimen (including both platinum and cetuximab) must be the most recent anti-neoplastic treatment regimen administered. * Patients with swallowing dysfunction who are unable to swallow BYL719 whole tablets and are not using feeding tubes for study drug administration can participate in the Phase Ib Arm B. For the Phase II, these patients with swallowing dysfunction may participate if able to drink the suspension and results of Arm B confirm the use of this method. Patients with swallowing dysfunction requiring G tube (G/PEG tube) for study drug administration may participate in Phase II if Arm C confirms dispersible tablet via G tube administration is permitted if the administration of drinkable suspension of BYL719 is allowed to be used in Phase II. * Availability of a representative tumor specimen. Patients enrolled in Arm 3 of Phase II must have disease sites amenable to biopsy unless prior agreement between Novartis and the Investigator. * At least one measurable or non-measurable lesion as per RECIST 1.1 criteria for patients in Phase Ib; Measurable disease as determined by RECIST v1.1 for Phase II patients * World Health Organization (WHO) Performance Status (PS) ≤ 2 * Adequate organ function * Negative serum pregnancy test.
Exclusion criteria
* Prior treatment with PI3K-inhibitors * Patients with a prior serious infusion reaction to cetuximab * Patients with uncontrolled CNS tumor metastatic involvement * Clinically significant cardiac disease or impaired cardiac function * Patients with diabetes mellitus * Impaired GI function or GI disease * History of another malignancy within 2 years prior to starting study treatment * Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | until disease progression or intolerable toxicity (approximately 6 months) | Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR \> 1) \< 10%, and the posterior median HR \< 0.7. |
| Phase Ib Arm B: Probability That Distribution of Dose Limiting Toxicities (DLTs) is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | until disease progression or intolerable toxicity (approximately 6 months) | Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm B (crushed film-coated tablets as an oral suspension with swallowing dysfunction). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR \> 1) \< 10%, and the posterior median HR \< 0.7. |
| For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days) | until disease progression or intolerable toxicity (approximately 6 months) | Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets) and arm B (BYL719 administered as a drinkable suspension in patients with swallowing dysfunction). 6 months is an approximate timeframe. |
| Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | approximately 6 months | Assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab. 6 months is an approximate timeframe. |
| Phase II Arm 3: Progression Free Survival (PFS) as Per RECIST V1.1 | approximately 6 months | Assessment of the anti-tumor activity of BYL719 in combination with cetuximab in patients resistant to platinum-based therapy and cetuximab. |
| Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | 6 months | Comparison of single-dose exposure of BYL719 dispersible tablet via G-tube in combination with cetuximab in RM HNSCC to that of Arm A (film-coated tables) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Non-Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | approximately 6 months | Scheme 1 (arm 3): Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm 3 (non-randomized arm) |
| Phase II: Randomized Overall Survival (OS) by Treatment | approximately 1 year | Scheme 1 (Arms 1 and 2): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab |
| Phase II: Non-Randomized Overall Survival (OS) by Treatment | approximately 1 year | Scheme 1 (Arm 3): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab |
| Phase II, Scheme 1 (Arm 2B): Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Approximately 6 months | Phase II: Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab. Complete response (CR); Partial response (PR); Stable disease (SD) |
| Phase II, Scheme 2 (Arm 2B): Overall Survival (OS) for the Cross-over | approximately 1 year | Phase II, Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab. |
| Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | 1 to 24 hours post dose (Day 1 Cycle 1) | Non compartmental PK parameters derived after single dose at Cycle 1 Day 1 |
| Phase Ib: Cmax for BYL719 by Treatment | Day 1 Cycle 1 | Non compartmental Cmax derived after single dose at Cycle 1 Day 1 |
| Phase Ib: Tmax for BYL719 by Treatment | Day 1 Cycle 1 | Non compartmental Cmax derived after single dose at Cycle 1 Day 1 |
| Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1 | approximately 6 months | Phase II, Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab |
| Phase Ib: Cmax for BYL719 After Continuous Dose Administration (Steady State) | Day 1 Cycle 1 | Non compartmental PK parameters derived after single dose at Cycle 1 Day 1 |
| Phase Ib: Tmax for BYL719 After Continuous Dose Administration (Steady State) | Day 1 Cycle 1 | Non compartmental PK parameters derived after single dose at Cycle 1 Day 1 |
| Phase Ib: Notable Abnormal Vital Signs by Treatment | approximately 6 months | Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm A, B and C. |
| Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | baseline, post baseline | Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm A, B and C. |
| For Phase II: Notable Abnormal Vital Signs by Treatment | approximately 6 months | Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm 1, 2 and 2B. |
| For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | baseline, post baseline during the entire study period (approximately 1 year) | Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm 1, 2 and 2B. |
| Phase II: Progression Free Survival (PFS) Based on Investigator's Assessment With Treatment | approximately 6 months | Assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab |
| Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State) | Day 1 Cycle 1 | Non compartmental PK parameters derived after single dose at Cycle 1 Day 1 |
| Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | approximately 6 months | Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm A, B and C. |
| For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | approximately 6 months | Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm A, B and C CR=complete response PR=partial response |
| Phase II: Randomized Best Overall Response as Per RECIST v1.1 | approximately 6 months | Scheme 1 (Arms 1 and 2): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab |
| Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1 | approximately 6 months | Scheme 1 (Arm 3): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab |
| Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | approximately 6 months | Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arms 1 and 2. |
Countries
Australia, Canada, France, Hong Kong, Netherlands, Singapore, South Korea, Taiwan, United States
Participant flow
Recruitment details
45 patients enrolled in Phase Ib, 106 cetuximab naïve patients in Phase II were randomized to either BYL719+cet (N=71) or cet monotherapy (N=35). Of the 35 patients, 16 crossed over to BYL719+cet combo treatment. 29 patients enrolled in the non-randomized combo treatment arm (cet resistant patients). All patients have completed the trial.
Pre-assignment details
One patient was prematurely randomized at the site but was never treated.
Participants by arm
| Arm | Count |
|---|---|
| Arm A - 300mg BYL719+Cetuximab 300 mg BYL719 as film-coated (FC) whole tablets with cetuximab. | 16 |
| Arm A - 400mg BYL719+Cetuximab 400 mg BYL719 as FC whole tablets with cetuximab | 5 |
| Arm B - BYL719 + Cetuximab, Oral Suspension 300mg BYL719 as crushed FC tablets with cetuxumab in patients with swallowing dysfunction | 18 |
| Arm C - BYL719+Cetuximab, Dispersible Tablets 300mg BYL719 dispersible tablets with cetuxumab in patients with swallowing dysfunction administered via G-tube | 6 |
| Arm 1 - BYL719+Cetuximab (Randomized) 300mg BYL719 with cetuxumab (Phase II) in patients resistant to or intolerant/ineligible for platinum-based chemotherapy. | 71 |
| Arm 2 - Monotherapy Cetuximab (Randomized) Cetuximab in Phase II in patients resistant to or intolerant/ineligible for platinum-based chemotherapy. | 35 |
| Arm 3 - BYL719+Cetuximab (Non-randomized) 300mg BYL719 with cetuximab in Phase II in patients resistant to platinum-based therapy and cetuximab | 29 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 | 5 | 4 | 15 | 3 | 9 |
| Overall Study | Cross-over patients to combo treatment | 0 | 0 | 0 | 0 | 0 | 16 | 0 |
| Overall Study | Death | 1 | 1 | 1 | 1 | 7 | 2 | 2 |
| Overall Study | Disease progression | 6 | 3 | 10 | 1 | 41 | 12 | 15 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 0 | 2 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Subject/guardian decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 | 0 | 6 | 0 | 1 |
Baseline characteristics
| Characteristic | Arm A - 300mg BYL719+Cetuximab | Arm A - 400mg BYL719+Cetuximab | Arm B - BYL719 + Cetuximab, Oral Suspension | Arm C - BYL719+Cetuximab, Dispersible Tablets | Arm 1 - BYL719+Cetuximab (Randomized) | Arm 2 - Monotherapy Cetuximab (Randomized) | Arm 3 - BYL719+Cetuximab (Non-randomized) | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 13.4 | 62.6 years STANDARD_DEVIATION 7.99 | 56.7 years STANDARD_DEVIATION 10.2 | 60.5 years STANDARD_DEVIATION 14.1 | 57.2 years STANDARD_DEVIATION 9.66 | 57.1 years STANDARD_DEVIATION 10.37 | 56.9 years STANDARD_DEVIATION 8.25 | 57.0 years STANDARD_DEVIATION 10.16 |
| Sex: Female, Male Female | 7 Participants | 1 Participants | 4 Participants | 2 Participants | 16 Participants | 4 Participants | 10 Participants | 44 Participants |
| Sex: Female, Male Male | 9 Participants | 4 Participants | 14 Participants | 4 Participants | 55 Participants | 31 Participants | 19 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 15 | 5 / 5 | 18 / 18 | 6 / 6 | 69 / 69 | 35 / 35 | 29 / 29 | 177 / 178 |
| serious Total, serious adverse events | 9 / 15 | 4 / 5 | 12 / 18 | 4 / 6 | 40 / 69 | 15 / 35 | 15 / 29 | 99 / 178 |
Outcome results
Primary
For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days)
Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets) and arm B (BYL719 administered as a drinkable suspension in patients with swallowing dysfunction). 6 months is an approximate timeframe.
Time frame: until disease progression or intolerable toxicity (approximately 6 months)
Population: Dose Determining Analysis Set (DDS) consisted of all patients from the SAS who met the requirements for minimum safety evaluation and minimum exposure or experienced DLT during Cycle 1. This analysis set was defined only for the Phase Ib patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days) | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days) | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days) | 4 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days) | 2 Participants |
| All Patients | For Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (28 Days) | 9 Participants |
Primary
Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment
Comparison of single-dose exposure of BYL719 dispersible tablet via G-tube in combination with cetuximab in RM HNSCC to that of Arm A (film-coated tables)
Time frame: 6 months
Population: Pharmacokinetic Analysis Set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data. The PAS was used for summaries of PK data as well as for listings of derived parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUCinf | 22600 hr*ng/mL |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUClast | 19200 hr*ng/mL |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUC0_24 | 18800 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUCinf | 24100 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUClast | 22100 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUC0_24 | 19400 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUC0_24 | 26300 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUCinf | 27800 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUClast | 26200 hr*ng/mL |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUCinf | 27300 hr*ng/mL |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUClast | 25000 hr*ng/mL |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Area Under Curve (AUC) 0-24 for BYL719 by Treatment | AUC0_24 | 25600 hr*ng/mL |
Primary
Phase Ib Arm B: Probability That Distribution of Dose Limiting Toxicities (DLTs) is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days)
Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm B (crushed film-coated tablets as an oral suspension with swallowing dysfunction). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR \> 1) \< 10%, and the posterior median HR \< 0.7.
Time frame: until disease progression or intolerable toxicity (approximately 6 months)
Population: Dose Determining Analysis Set (DDS) consisted of all patients from the SAS who met the requirements for minimum safety evaluation and minimum exposure or experienced DLT during Cycle 1. This analysis set was defined only for the Phase Ib patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib Arm B: Probability That Distribution of Dose Limiting Toxicities (DLTs) is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr(DLT) in 0-0.16 | 0.267 Probability of DLT rate |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib Arm B: Probability That Distribution of Dose Limiting Toxicities (DLTs) is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr (DLT) in 0.16-0.35 | 0.664 Probability of DLT rate |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib Arm B: Probability That Distribution of Dose Limiting Toxicities (DLTs) is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr (DLT) in 0.35-1 | 0.069 Probability of DLT rate |
Primary
Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days)
Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) of BYL719 in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) in arm A (BYL719 administered as a whole tablet in patients able to swallow the tablets). Dose recommendation was based on posterior summaries including the mean, median, standard deviation, 95%-credibility interval, and the probability that the true DLT rate for each dose combination lies in one of the following categories: (0%, 16%) under-dosing; (16%, 35%) targeted toxicity; (35%, 100%) excessive toxicity. The combination treatment was considered superior to cetuximab alone if the posterior probability (HR \> 1) \< 10%, and the posterior median HR \< 0.7.
Time frame: until disease progression or intolerable toxicity (approximately 6 months)
Population: Dose Determining Analysis Set (DDS) consisted of all patients from the SAS who met the requirements for minimum safety evaluation and minimum exposure or experienced DLT during Cycle 1. This analysis set was defined only for the Phase Ib patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr(DLT) in 0-0.16 | 0.764 Probability of DLT rate |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr (DLT) in 0.16-0.35 | 0.222 Probability of DLT rate |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr (DLT) in 0.35-1 | 0.015 Probability of DLT rate |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr(DLT) in 0-0.16 | 0.086 Probability of DLT rate |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr (DLT) in 0.16-0.35 | 0.376 Probability of DLT rate |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib Arms A: Probability That Dose Limiting Toxicities (DLTs) Rate is in the Recommended Phase 2 Dose in Cycle 1 (Cycle 1=28 Days) | Posterior probabilities that Pr (DLT) in 0.35-1 | 0.538 Probability of DLT rate |
Primary
Phase II Arm 3: Progression Free Survival (PFS) as Per RECIST V1.1
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab in patients resistant to platinum-based therapy and cetuximab.
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II Arm 3: Progression Free Survival (PFS) as Per RECIST V1.1 | 3.896 months |
Primary
Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab. 6 months is an approximate timeframe.
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Number of PFS events | 46 participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Progression | 33 participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Number of censored | 25 participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Death | 13 participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Death | 2 participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Number of PFS events | 27 participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Number of censored | 8 participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II Arms 1 and 2: Progression Free Survival (PFS) as Per RECIST v1.1 by Central Radiology Review | Progression | 25 participants |
Comparison: The hazard ratio was estimated using the Bayesian Cox proportional hazard (PH) model.
p-value: 0.64395% CI: [0.69, 1.82]Regression, Cox
Comparison: Adjusted on Covariates: treatment, sum of longest diameters from central data \[SLD (C)\], Hemaglobin (Hgb) and White Blood Cells (WBC).p-value: 0.03995% CI: [0.3, 0.97]Regression, Cox
Secondary
For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm A, B and C CR=complete response PR=partial response
Time frame: approximately 6 months
Population: Safety Analysis Set (SAS) consisted of all patients from the FAS who received at least one dose of BYL719 or the standard cetuximab therapy and had at least one post -baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | ORR (CR) or PR) | 25.5 Percentages |
| Arm A - 300mg BYL719+Cetuximab | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR (CR or PR or Stable Disease or non-CR/Non-PD) | 75.0 Percentages |
| Arm A - 400mg BYL719+Cetuximab | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | ORR (CR) or PR) | 0.0 Percentages |
| Arm A - 400mg BYL719+Cetuximab | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR (CR or PR or Stable Disease or non-CR/Non-PD) | 20.0 Percentages |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | ORR (CR) or PR) | 0.0 Percentages |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR (CR or PR or Stable Disease or non-CR/Non-PD) | 50.0 Percentages |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR (CR or PR or Stable Disease or non-CR/Non-PD) | 16.7 Percentages |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | ORR (CR) or PR) | 0.0 Percentages |
| All Patients | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | ORR (CR) or PR) | 8.9 Percentages |
| All Patients | For Phase Ib: Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR (CR or PR or Stable Disease or non-CR/Non-PD) | 51.1 Percentages |
Secondary
For Phase II: Notable Abnormal Vital Signs by Treatment
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm 1, 2 and 2B.
Time frame: approximately 6 months
Population: Safety Analysis Set (SAS) consisted of all patients from the FAS who received at least one dose of BYL719 or the standard cetuximab therapy and had at least one post -baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): High only | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High only | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): Low only | 11 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): Low only | 4 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): Low only | 2 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High and low | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High and low | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High only | 4 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High only | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): Low only | 3 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): Low only | 31 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High only | 2 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): Low only | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): High only | 4 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): Low only | 3 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): Low only | 3 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): Low only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): Low only | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High only | 3 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High only | 2 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): Low only | 3 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): Low only | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High only | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High only | 5 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): Low only | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): Low only | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): Low only | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): Low only | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): High only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): Low only | 9 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High only | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): Low only | 4 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Notable Abnormal Vital Signs by Treatment | Weight (kg): High and low | 0 Participants |
Secondary
For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm 1, 2 and 2B.
Time frame: baseline, post baseline during the entire study period (approximately 1 year)
Population: Safety Analysis Set (SAS) consisted of all patients from the FAS who received at least one dose of BYL719 or the standard cetuximab therapy and had at least one post -baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 30 | 35 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 60 | 6 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 30 | 40 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 60 | 7 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 30 | 43 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 60 | 17 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR > 100 | 9 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR < 50 | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | PR (msec): increase > 25% & to a VR > 200 | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QRS (msec): increase > 25% & to a VR > 110 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | PR (msec): increase > 25% & to a VR > 200 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 30 | 4 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 60 | 2 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 30 | 13 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 60 | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QRS (msec): increase > 25% & to a VR > 110 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR < 50 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 30 | 12 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR > 100 | 4 Participants |
| Arm A - 400mg BYL719+Cetuximab | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 60 | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR < 50 | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 60 | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 30 | 23 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 60 | 5 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | PR (msec): increase > 25% & to a VR > 200 | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR > 100 | 3 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 30 | 15 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QRS (msec): increase > 25% & to a VR > 110 | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 60 | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | For Phase II: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 30 | 15 Participants |
Secondary
Phase Ib: Cmax for BYL719 After Continuous Dose Administration (Steady State)
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Time frame: Day 1 Cycle 1
Population: Pharmacokinetic Analysis Set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data. The PAS was used for summaries of PK data as well as for listings of derived parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Cmax for BYL719 After Continuous Dose Administration (Steady State) | 2200 ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Cmax for BYL719 After Continuous Dose Administration (Steady State) | 2820 ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Cmax for BYL719 After Continuous Dose Administration (Steady State) | 2750 ng/mL |
Secondary
Phase Ib: Cmax for BYL719 by Treatment
Non compartmental Cmax derived after single dose at Cycle 1 Day 1
Time frame: Day 1 Cycle 1
Population: Pharmacokinetic Analysis Set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data. The PAS was used for summaries of PK data as well as for listings of derived parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Cmax for BYL719 by Treatment | 2130 ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Cmax for BYL719 by Treatment | 2370 ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Cmax for BYL719 by Treatment | 2010 ng/mL |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Cmax for BYL719 by Treatment | 2520 ng/mL |
Secondary
Phase Ib: Notable Abnormal Vital Signs by Treatment
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm A, B and C.
Time frame: approximately 6 months
Population: Safety Analysis Set (SAS) consisted of all patients from the FAS who received at least one dose of BYL719 or the standard cetuximab therapy and had at least one post -baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): Low only | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): Low only | 7 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High only | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): Low only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High and low | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): Low only | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): Low only | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): Low only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): Low only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): Low only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): Low only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): Low only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): Low only | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High and low | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): Low only | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): Low only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): Low only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High only | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): Low only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): Low only | 3 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High only | 4 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High and low | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): Low only | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High only | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High and low | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): Low only | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High only | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High and low | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High only | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High only | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): Low only | 3 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High only | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High only | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High only | 4 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): Low only | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): Low only | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): Low only | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): High and low | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High and low | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Body Temperature (Celsius): High and low | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting Pulse rate (bpm): High and low | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting systolic B.P. (mmHg): High and low | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): High and low | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Weight (kg): High only | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Sitting diastolic B.P. (mmHg): Low only | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Notable Abnormal Vital Signs by Treatment | Respiratory Rate (bpm): Low only | 0 Participants |
Secondary
Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities
Characterization of the safety and tolerability of BYL719 in combination with cetuximab in arm A, B and C.
Time frame: baseline, post baseline
Population: Safety Analysis Set (SAS) consisted of all patients from the FAS who received at least one dose of BYL719 or the standard cetuximab therapy and had at least one post -baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 30 | 9 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 60 | 2 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 30 | 11 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 60 | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 30 | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 60 | 4 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR > 100 | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR < 50 | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | PR (msec): increase > 25% & to a VR > 200 | 0 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QRS (msec): increase > 25% & to a VR > 110 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 30 | 4 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | PR (msec): increase > 25% & to a VR > 200 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 60 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 30 | 4 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 60 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR > 100 | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QRS (msec): increase > 25% & to a VR > 110 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR < 50 | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 30 | 4 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 60 | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR < 50 | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR > 100 | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QRS (msec): increase > 25% & to a VR > 110 | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 30 | 10 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 60 | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 60 | 3 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | PR (msec): increase > 25% & to a VR > 200 | 0 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 60 | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 30 | 10 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 30 | 12 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 30 | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR < 50 | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QT (msec): Increase from baseline > 60 | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QRS (msec): increase > 25% & to a VR > 110 | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | VR (bpm): RR decrease > 25% & to a VR > 100 | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 60 | 0 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 30 | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcB (msec): Increase from baseline > 60 | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | QTcF (msec): Increase from baseline > 30 | 1 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Number of Patients With Notable Electrocardiogram (ECG) Abnormalities | PR (msec): increase > 25% & to a VR > 200 | 0 Participants |
Secondary
Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State)
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Time frame: Day 1 Cycle 1
Population: Pharmacokinetic Analysis Set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data. The PAS was used for summaries of PK data as well as for listings of derived parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State) | AUC (0-24) | 24600 hr*ng/mL |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State) | AUClast | 24500 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State) | AUC (0-24) | 28500 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State) | AUClast | 2370 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State) | AUC (0-24) | 30500 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Plasma Pharmacokinetic Parameters for BYL719 After Continuous Dose Administration (Steady State) | AUClast | 22100 hr*ng/mL |
Secondary
Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Time frame: 1 to 24 hours post dose (Day 1 Cycle 1)
Population: Pharmacokinetic Analysis Set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data. The PAS was used for summaries of PK data as well as for listings of derived parameters.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUCinf | 22600 hr*ng/mL |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUClast | 19200 hr*ng/mL |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUC0_24 | 18800 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUCinf | 27300 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUClast | 2370 hr*ng/mL |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUC0_24 | 25600 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUC0_24 | 19400 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUCinf | 24100 hr*ng/mL |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUClast | 22100 hr*ng/mL |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUCinf | 27800 hr*ng/mL |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUClast | 26200 hr*ng/mL |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Primary Plasma Pharmacokinetic Parameters for BYL719 by Treatment | AUC0_24 | 26300 hr*ng/mL |
Secondary
Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1
Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm A, B and C.
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Progression) | 5 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | Number of Censored | 9 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Death) | 2 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Progression) | 2 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | Number of Censored | 1 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Death) | 2 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Death) | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Progression) | 10 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | Number of Censored | 7 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Progression) | 2 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | Number of Censored | 3 Participants |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Progression Free Survival (PFS) as Per RECIST v1.1 | PFS event (Death) | 1 Participants |
Secondary
Phase Ib: Tmax for BYL719 After Continuous Dose Administration (Steady State)
Non compartmental PK parameters derived after single dose at Cycle 1 Day 1
Time frame: Day 1 Cycle 1
Population: Pharmacokinetic Analysis Set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data. The PAS was used for summaries of PK data as well as for listings of derived parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Tmax for BYL719 After Continuous Dose Administration (Steady State) | 3.15 hr |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Tmax for BYL719 After Continuous Dose Administration (Steady State) | 3.15 hr |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Tmax for BYL719 After Continuous Dose Administration (Steady State) | 1 hr |
Secondary
Phase Ib: Tmax for BYL719 by Treatment
Non compartmental Cmax derived after single dose at Cycle 1 Day 1
Time frame: Day 1 Cycle 1
Population: Pharmacokinetic Analysis Set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data. The PAS was used for summaries of PK data as well as for listings of derived parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase Ib: Tmax for BYL719 by Treatment | 2.02 hr |
| Arm A - 400mg BYL719+Cetuximab | Phase Ib: Tmax for BYL719 by Treatment | 2.97 hr |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase Ib: Tmax for BYL719 by Treatment | 3 hr |
| Arm C - BYL719+Cetuximab, Dispersible Tablets | Phase Ib: Tmax for BYL719 by Treatment | 2.23 hr |
Secondary
Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1
Scheme 1 (Arm 3): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1 | Complete Response (CR) | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1 | Partial Response (PR) | 2 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1 | Stable Disease (SD) | 8 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1 | Progressive Disease (PD) | 5 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1 | Non-CR/Non-PD (NCRNPD) | 6 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Best Overall Response as Per RECIST v1.1 | Unknown | 7 Participants |
Secondary
Phase II: Non-Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Scheme 1 (arm 3): Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arm 3 (non-randomized arm)
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Overall response rate (ORR) (CR or PR) | 10.3 Percentages |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Disease control rate 1 (DCR 1) (CR or PR or SD) | 37.9 Percentages |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR 2 (CR or PR or SD or Non-CR/Non-PD) | 58.6 Percentages |
Secondary
Phase II: Non-Randomized Overall Survival (OS) by Treatment
Scheme 1 (Arm 3): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Time frame: approximately 1 year
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Overall Survival (OS) by Treatment | Number of deaths | 13 Patients |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Non-Randomized Overall Survival (OS) by Treatment | Number of censored | 10 Patients |
95% CI: [172, 463]
Secondary
Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1
Phase II, Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab
Time frame: approximately 6 months
Population: Full analysis Set (FAS) consisted of those patients who, after crossing over had received at least one dose of BYL719.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1 | Number of PFS | 12 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1 | Progression | 9 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1 | Death | 3 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Progression Free Survival (PFS) as Per RECIST v 1.1 | Number of Censored | 4 Participants |
95% CI: [27, 88]
Secondary
Phase II: Progression Free Survival (PFS) Based on Investigator's Assessment With Treatment
Assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Progression Free Survival (PFS) Based on Investigator's Assessment With Treatment | 94.0 Days |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Progression Free Survival (PFS) Based on Investigator's Assessment With Treatment | 85.0 Days |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Progression Free Survival (PFS) Based on Investigator's Assessment With Treatment | 117.0 Days |
p-value: 0.23595% CI: [0.49, 1.19]Regression, Cox
Comparison: Adjusted on Covariates: treatment, sum of longest diameters from local data \[SLD (L)\], Hemaglobin (Hgb) and White Blood Cells (WBC).p-value: 0.06295% CI: [0.4, 1.02]Regression, Cox
Secondary
Phase II: Randomized Best Overall Response as Per RECIST v1.1
Scheme 1 (Arms 1 and 2): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Complete Response | 1 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Partial Response | 6 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Stable Disease | 24 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Progressive Disease | 17 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Non-CR/Non-PD (NCRNPD) | 6 Participants |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Unknown | 17 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Unknown | 3 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Complete Response | 0 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Progressive Disease | 12 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Non-CR/Non-PD (NCRNPD) | 10 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Partial Response | 2 Participants |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Stable Disease | 8 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Partial Response | 8 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Stable Disease | 32 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Unknown | 20 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Progressive Disease | 29 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Complete Response | 1 Participants |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Best Overall Response as Per RECIST v1.1 | Non-CR/Non-PD (NCRNPD) | 16 Participants |
Secondary
Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Assessment of the preliminary anti-tumor activity of BYL719 in combination with cetuximab in arms 1 and 2.
Time frame: approximately 6 months
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Disease control rate 1 (DCR 1) (CR or PR or SD) | 43.7 Percentages |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Overall response rate (ORR) (CR or PR) | 9.9 Percentages |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR 2 (CR or PR or SD or Non-CR/Non-PD) | 52.1 Percentages |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Disease control rate 1 (DCR 1) (CR or PR or SD) | 28.6 Percentages |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Overall response rate (ORR) (CR or PR) | 5.7 Percentages |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR 2 (CR or PR or SD or Non-CR/Non-PD) | 57.1 Percentages |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Overall response rate (ORR) (CR or PR) | 8.5 Percentages |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | DCR 2 (CR or PR or SD or Non-CR/Non-PD) | 53.8 Percentages |
| Arm B - BYL719 + Cetuximab, Oral Suspension | Phase II: Randomized Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Disease control rate 1 (DCR 1) (CR or PR or SD) | 38.7 Percentages |
Secondary
Phase II: Randomized Overall Survival (OS) by Treatment
Scheme 1 (Arms 1 and 2): Further assessment of the anti-tumor activity of BYL719 in combination with cetuximab vs. cetuximab as single-agent in RM HNSCC patients naive to cetuximab
Time frame: approximately 1 year
Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of either BYL719 or Cetuximab in Phase Ib and Phase II Arm 3, and all randomized patients in Phase II Scheme 1, Arm 1 and Arm 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Overall Survival (OS) by Treatment | Number of deaths | 51 Patients |
| Arm A - 300mg BYL719+Cetuximab | Phase II: Randomized Overall Survival (OS) by Treatment | Number of censored | 20 Patients |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Overall Survival (OS) by Treatment | Number of deaths | 26 Patients |
| Arm A - 400mg BYL719+Cetuximab | Phase II: Randomized Overall Survival (OS) by Treatment | Number of censored | 9 Patients |
p-value: 0.31395% CI: [0.79, 2.05]Regression, Cox
Secondary
Phase II, Scheme 1 (Arm 2B): Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1
Phase II: Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab. Complete response (CR); Partial response (PR); Stable disease (SD)
Time frame: Approximately 6 months
Population: Safety Analysis Set (SAS) consisted of all patients from the FAS who received at least one dose of BYL719 or the standard cetuximab therapy and had at least one post -baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II, Scheme 1 (Arm 2B): Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Overall Response (ORR) - CR or PR | 0 Rate |
| Arm A - 300mg BYL719+Cetuximab | Phase II, Scheme 1 (Arm 2B): Overall Response Rate (ORR) and Disease Control Rate (DCR) as Per RECIST v1.1 | Disease Control Rate (DCR) - CR, PR, or SD | 25.0 Rate |
Secondary
Phase II, Scheme 2 (Arm 2B): Overall Survival (OS) for the Cross-over
Phase II, Scheme 1 (Arm 2B): To further assess the anti-tumor activity of BYL719 + cetuximab in the setting of resistance to single agent cetuximab.
Time frame: approximately 1 year
Population: Safety Analysis Set (SAS) consisted of all patients from the FAS who received at least one dose of BYL719 or the standard cetuximab therapy and had at least one post -baseline safety assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - 300mg BYL719+Cetuximab | Phase II, Scheme 2 (Arm 2B): Overall Survival (OS) for the Cross-over | 96.0 Days |