Non-small-cell Lung Cancer
Conditions
Keywords
Non-small-cell lung cancer, HSP90, 2nd to 3rd line treatment
Brief summary
This study will assess the efficacy of AUY922, when administered weekly at 70 mg/m2, in adult patients with advanced Non-small-cell Lung Cancer (NSCLC), who have received at least two prior lines of chemotherapy. Patients will be retrospectively, and prospectively, stratified based on their molecular tumor etiology. The following strata was assigned: Patients with Epidermal growth factor receptor (EGFR) activating mutations, Patients with Kirstin Raus sarcoma virus (KRAS) activating mutations, Patients with EML4-ALK (anaplastic lymphoma kinase) translocations and patients that were both EGFR and Kras wild type.
Interventions
DRUGAUY922
AUY922 was supplied in individual 10 mL amber colored glass ampoules containing 10 mL of a 5 mg/mL active drug substance in 5% aqueous glucose solution. AUY922 was administered intravenously (i.v.) weekly at 70 mg/m2.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically or cytologically confirmed advanced (stage IIIB or stage IV) NSCLC who have received at least two prior lines of treatment. Patients who, in the investigators opinion, are deemed unsuitable for the standard 2nd line chemotherapy will be eligible for protocol participation. One of the prior lines must have included a platinum agent. Prior treatment with a platinum agent is not a requirement for EGFR mutant patients and patients with EML4-ALK translocations * Patients enrolled to the fifth stratum, modified EGFR mutant, must have documented prior response to EGFR TKI as defined by CR, PR or SD for 6 months or greater unless patient has de novo resistance to EGFR TKI (e.g. exon 20 insertions.) * All patients must have at least one measurable lesion as defined by RECIST criteria. Previously irradiated lesions are not measurable unless the lesion is new or has demonstrated clear progression after radiation * World Health Organization (WHO) performance status ≤ 2. For patients enrolled to the fifth stratum, modified EGFR mutant, World Health Organization (WHO) performance status ≤ 1 * Patients enrolled to the fifth stratum, modified EGFR mutant, must be willing and suitable to undergo fresh baseline biopsy prior to study treatment (unless patient had recent biopsy after EGFR TKI progression that concluded resistance to EGFR TKI.) * Hematologic: * Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L. * Hemoglobin (Hgb) ≥ 9 g/dl. * Platelets (plt) ≥ 100 x 109/L. Biochemistry: * Total calcium (corrected for serum albumin) within normal limits or correctable with supplements. * Magnesium within lower normal limits or correctable with supplements. Adequate liver function defined as: * AST/SGOT and ALT/SGPT ≤ 3.0 x Upper limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastasis are present. * Serum bilirubin ≤ 1.5 x ULN. * Serum albumin \> 2.5 g/dL. * Serum creatinine ≤ 1.5 x ULN or 24 hour clearance ≥ 50 mL/min.
Exclusion criteria
* Patients who have received more than four lines of prior treatment. Exception: Patients enrolled to the fifth stratum, modified EGFR mutant, must not have received more than two prior lines of therapy. Chemotherapy administered as adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study. * Patients with a history of CNS metastasis. Note: Patients without clinical signs and symptoms of CNS involvement are not required to have MRI of the brain. Exception: Patients with treated brain metastases who are asymptomatic, who has discontinued corticosteroids, and who have been clinically stable for one month will be eligible for protocol participation. This exception is not valid for patients enrolled to the fifth stratum, modified EGFR mutant. These patients must not have CNS involvement. * Prior anti-neoplastic treatment with any HSP90 or HDAC inhibitor compound. * Patients must not have received: * any systemic anti-cancer treatment or radiotherapy within 4 weeks prior to first dose of study treatment and should have recovered to baseline or less than Grade 1 from toxicities of such therapy prior to the first dose of study treatment * 2 weeks for palliative radiotherapy to bones, 6 weeks for nitrosoureas and mitomycin * 4 weeks for monoclonal antibodies * and ≤5 half-life of the agent or active metabolites \[if any\] for continuous systemic anti-cancer treatment or investigational * Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Assessment by Study Stratum - Per Investigator Assessment | 18 weeks | The primary endpoint of the study was the investigator assessment of efficacy at 18 weeks in terms of response complete response (CR)/partial response (PR), stable disease (SD), or non clinical benefit (NCB) as assessed by response evaluation criteriain solid tumors (RECIST) version 1.0. ORR = patients with confirmed complete or partial response. Stable disease at 18 weeks = patients without response and with no assessment of progressive disease up to 18 weeks, but with an assessment of stable disease or better either within 2 weeks prior to the 18 week time point, or at the next non-missing assessment after the 18 week time point. No clinical benefit = all other patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | Week 12, Week 18 | Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact. |
| Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | Week 12, Week 18 | Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient did not have an event, progression-free survival was censored at the date of last adequate tumor assessment. A Novartis modified response evaluation criteria in solid tumors RECIST 1.1 criteria was applied to CT/MRI imaging data when assessing any responses to AUY922 treatment. All images were evaluated locally by the investigator. All complete or partial responses were confirmed by a second assessment at least 4 weeks later. |
| Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf | 1 hour after infusion | Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve infinity. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed. |
| Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast | 1 hour after infusion | Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve last. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed. |
| Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax | 1 hour after infusion | Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for concentration max. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed. |
Countries
Canada, France, Germany, Netherlands, Norway, Singapore, South Korea, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
Two patients who were ongoing at the data cut-off of 30-Jul-2013 are considered as 'completed' in this study.
Participants by arm
| Arm | Count |
|---|---|
| Kras Mutant Patients Patients with KRAS mutant tumors. Patients received AUY922 at 70 mg/m\^2 weekly infusions. | 28 |
| EGFR Mutant Patients Patients with EGFR activating mutation tumors (Note: These patients must have progressed on one prior EGFR TKI containing regimen unless they have documented T790M activating mutation). Patients received AUY922 at 70 mg/m\^2 weekly infusions. | 35 |
| EGFR and Kras Wild Type Patients Patients exhibiting both mutations were stratified to the KRAS mutation stratum. Patients received AUY922 at 70 mg/m\^2 weekly infusions. | 34 |
| Patients With EML4-ALK Translocation Patients with NSCLC who have tumors with an inversion in the short arm of chromosome 2 that results in the fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene leading to the production of an EML4-ALK fusion tyrosine kinase. ALK is a transmembrane protein, which has a kinase domain and is not usually expressed in the lung. EML4 mediate ligand-independent dimerization, and therefore constitutive activity of the ALK tyrosine kinase domain. Patients received AUY922 at 70 mg/m\^2 weekly infusions. | 22 |
| Modified EGFR Mutant Patients The modified EGFR stratum was defined as patients less heavily pretreated who had received one or two lines of prior therapy, with a documented response to a EGFR tyrosine kinase inhibitor (TKI) (complete response (CR), partial response (PR) or stable disease (SD) for ≥ 6 months), unless the patient had de novo resistance to EGFR TKI. Patients received AUY922 at 70 mg/m\^2 weekly infusions. | 31 |
| Unknown For some patients, it was not possible to determine their genotype, and hence their stratum membership could not be determined. Patients received AUY922 at 70 mg/m\^2 weekly infusions. | 3 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 6 | 9 | 6 | 2 | 1 | 0 |
| Overall Study | Follow up phase competed as per protocol | 18 | 22 | 24 | 18 | 26 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 4 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | EGFR Mutant Patients | Total | Unknown | Modified EGFR Mutant Patients | Kras Mutant Patients | Patients With EML4-ALK Translocation | EGFR and Kras Wild Type Patients |
|---|---|---|---|---|---|---|---|
| Age, Customized < 65 years | 21 Participants | 108 Participants | 1 Participants | 25 Participants | 20 Participants | 18 Participants | 23 Participants |
| Age, Customized >= 65 years | 14 Participants | 45 Participants | 2 Participants | 6 Participants | 8 Participants | 4 Participants | 11 Participants |
| Body surface area | 1.7 m^2 STANDARD_DEVIATION 0.18 | 1.8 m^2 STANDARD_DEVIATION 0.21 | 1.9 m^2 STANDARD_DEVIATION 0.27 | 1.8 m^2 STANDARD_DEVIATION 0.18 | 1.9 m^2 STANDARD_DEVIATION 0.23 | 1.7 m^2 STANDARD_DEVIATION 0.2 | 1.8 m^2 STANDARD_DEVIATION 0.21 |
| Height | 163.0 cm STANDARD_DEVIATION 6.63 | 165.7 cm STANDARD_DEVIATION 9.49 | 173.0 cm STANDARD_DEVIATION 14.73 | 163.9 cm STANDARD_DEVIATION 8.93 | 170.5 cm STANDARD_DEVIATION 9.94 | 164.9 cm STANDARD_DEVIATION 9.8 | 165.8 cm STANDARD_DEVIATION 10.32 |
| Percentage of LVEF (left ventricular ejection fraction) | 66.9 Percentage of LVEF STANDARD_DEVIATION 7.63 | 66.2 Percentage of LVEF STANDARD_DEVIATION 8.51 | 69.0 Percentage of LVEF STANDARD_DEVIATION 10.54 | 65.4 Percentage of LVEF STANDARD_DEVIATION 7.64 | 63.2 Percentage of LVEF STANDARD_DEVIATION 8.92 | 69.5 Percentage of LVEF STANDARD_DEVIATION 8.68 | 66.2 Percentage of LVEF STANDARD_DEVIATION 9.27 |
| Race/Ethnicity, Customized Asian | 10 Participants | 41 Participants | 1 Participants | 13 Participants | 2 Participants | 6 Participants | 9 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 25 Participants | 107 Participants | 2 Participants | 16 Participants | 25 Participants | 16 Participants | 23 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 4 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 25 Participants | 88 Participants | 0 Participants | 19 Participants | 11 Participants | 15 Participants | 18 Participants |
| Sex: Female, Male Male | 10 Participants | 65 Participants | 3 Participants | 12 Participants | 17 Participants | 7 Participants | 16 Participants |
| Smoking status Current smoker | 1 Participants | 10 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants |
| Smoking status Ex-smoker | 12 Participants | 72 Participants | 0 Participants | 16 Participants | 21 Participants | 5 Participants | 18 Participants |
| Smoking status Never smoked | 22 Participants | 71 Participants | 2 Participants | 14 Participants | 4 Participants | 15 Participants | 14 Participants |
| Time since smoking cessation | 176.6 months STANDARD_DEVIATION 15.04 | 152.4 months STANDARD_DEVIATION 142.22 | NA months | 340.4 months STANDARD_DEVIATION 179.18 | 59.0 months STANDARD_DEVIATION 80.65 | NA months | 180.3 months STANDARD_DEVIATION 120.88 |
| Weight | 64.0 kg STANDARD_DEVIATION 12.05 | 67.3 kg STANDARD_DEVIATION 13.7 | 76.6 kg STANDARD_DEVIATION 15.75 | 67.1 kg STANDARD_DEVIATION 11.02 | 74.5 kg STANDARD_DEVIATION 16.22 | 60.5 kg STANDARD_DEVIATION 12.3 | 68.4 kg STANDARD_DEVIATION 13.49 |
| Weight category 55 - <75 kg | 19 Participants | 84 Participants | 2 Participants | 20 Participants | 13 Participants | 9 Participants | 21 Participants |
| Weight category < 55 kg | 10 Participants | 32 Participants | 0 Participants | 4 Participants | 4 Participants | 10 Participants | 4 Participants |
| Weight category >= 75 kg | 6 Participants | 37 Participants | 1 Participants | 7 Participants | 11 Participants | 3 Participants | 9 Participants |
| WHO Performance status Who Performance status: 0 | 13 Participants | 54 Participants | 1 Participants | 11 Participants | 10 Participants | 9 Participants | 10 Participants |
| WHO Performance status Who Performance status: 1 | 19 Participants | 91 Participants | 2 Participants | 20 Participants | 18 Participants | 11 Participants | 21 Participants |
| WHO Performance status Who Performance status: 2 | 3 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 28 | 35 / 35 | 33 / 34 | 22 / 22 | 31 / 31 | 3 / 3 |
| serious Total, serious adverse events | 17 / 28 | 18 / 35 | 22 / 34 | 6 / 22 | 11 / 31 | 2 / 3 |
Outcome results
Primary
Response Assessment by Study Stratum - Per Investigator Assessment
The primary endpoint of the study was the investigator assessment of efficacy at 18 weeks in terms of response complete response (CR)/partial response (PR), stable disease (SD), or non clinical benefit (NCB) as assessed by response evaluation criteriain solid tumors (RECIST) version 1.0. ORR = patients with confirmed complete or partial response. Stable disease at 18 weeks = patients without response and with no assessment of progressive disease up to 18 weeks, but with an assessment of stable disease or better either within 2 weeks prior to the 18 week time point, or at the next non-missing assessment after the 18 week time point. No clinical benefit = all other patients.
Time frame: 18 weeks
Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Kras Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Stable disease for ≥18 weeks | 2 Participants |
| Kras Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Overall respose rate (ORR) | 0 Participants |
| Kras Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | No clinical benefit | 26 Participants |
| EGFR Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Stable disease for ≥18 weeks | 3 Participants |
| EGFR Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Overall respose rate (ORR) | 6 Participants |
| EGFR Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | No clinical benefit | 26 Participants |
| EGFR and Kras Wild Type Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Stable disease for ≥18 weeks | 3 Participants |
| EGFR and Kras Wild Type Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Overall respose rate (ORR) | 3 Participants |
| EGFR and Kras Wild Type Patients | Response Assessment by Study Stratum - Per Investigator Assessment | No clinical benefit | 28 Participants |
| Patients With EML4-ALK Translocation | Response Assessment by Study Stratum - Per Investigator Assessment | Stable disease for ≥18 weeks | 2 Participants |
| Patients With EML4-ALK Translocation | Response Assessment by Study Stratum - Per Investigator Assessment | Overall respose rate (ORR) | 7 Participants |
| Patients With EML4-ALK Translocation | Response Assessment by Study Stratum - Per Investigator Assessment | No clinical benefit | 13 Participants |
| Modified EGFR Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Stable disease for ≥18 weeks | 7 Participants |
| Modified EGFR Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | Overall respose rate (ORR) | 3 Participants |
| Modified EGFR Mutant Patients | Response Assessment by Study Stratum - Per Investigator Assessment | No clinical benefit | 21 Participants |
| Unknown | Response Assessment by Study Stratum - Per Investigator Assessment | Overall respose rate (ORR) | 1 Participants |
| Unknown | Response Assessment by Study Stratum - Per Investigator Assessment | No clinical benefit | 2 Participants |
| Unknown | Response Assessment by Study Stratum - Per Investigator Assessment | Stable disease for ≥18 weeks | 0 Participants |
Secondary
Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review
Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact.
Time frame: Week 12, Week 18
Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Kras Mutant Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 55.9 Percentage of participants |
| Kras Mutant Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 68.7 Percentage of participants |
| EGFR Mutant Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 74.1 Percentage of participants |
| EGFR Mutant Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 77.0 Percentage of participants |
| EGFR and Kras Wild Type Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 72.3 Percentage of participants |
| EGFR and Kras Wild Type Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 78.6 Percentage of participants |
| Patients With EML4-ALK Translocation | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 90.7 Percentage of participants |
| Patients With EML4-ALK Translocation | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 71.6 Percentage of participants |
| Modified EGFR Mutant Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 96.7 Percentage of participants |
| Modified EGFR Mutant Patients | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 93.3 Percentage of participants |
| Unknown | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 33.3 Percentage of participants |
| Unknown | Overall Survival Rate Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 66.7 Percentage of participants |
Secondary
Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf
Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve infinity. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
Time frame: 1 hour after infusion
Population: PK analysis subset - All patients who received at least one dose of AUY922 in Cycle 1 and had at least one measurable post-dose AUY922 concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kras Mutant Patients | Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf | 2101.27 h*ng/mL | Standard Deviation 990.32 |
| EGFR Mutant Patients | Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUCinf | 13963.07 h*ng/mL | Standard Deviation 13006.537 |
Secondary
Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast
Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for area under the curve last. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
Time frame: 1 hour after infusion
Population: PK analysis subset - All patients who received at least one dose of AUY922 in Cycle 1 and had at least one measurable post-dose AUY922 concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kras Mutant Patients | Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast | 1997.04 h*ng/mL | Standard Deviation 894.903 |
| EGFR Mutant Patients | Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: AUClast | 12496.75 h*ng/mL | Standard Deviation 12035.525 |
Secondary
Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax
Summary of PK parameters for all patients one hour post 70 mg/m2 AUY922 infusion for concentration max. There are discrepancies between sample numbers and study population because PK samples were not collected from all study subjects and thus were not analyzed.
Time frame: 1 hour after infusion
Population: PK analysis subset - All patients who received at least one dose of AUY922 in Cycle 1 and had at least one measurable post-dose AUY922 concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kras Mutant Patients | Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax | 1130.59 ng/mL | Standard Deviation 705.177 |
| EGFR Mutant Patients | Pharmacokinetics (PK) of Plasma Concentration of AUY922 and Its Metabolite BJP762: Cmax | 2332.86 ng/mL | Standard Deviation 1377.35 |
Secondary
Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient did not have an event, progression-free survival was censored at the date of last adequate tumor assessment. A Novartis modified response evaluation criteria in solid tumors RECIST 1.1 criteria was applied to CT/MRI imaging data when assessing any responses to AUY922 treatment. All images were evaluated locally by the investigator. All complete or partial responses were confirmed by a second assessment at least 4 weeks later.
Time frame: Week 12, Week 18
Population: The Full Analysis Set (FAS) consisted of all patients who received at least one dose of AUY922.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Kras Mutant Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 31.5 Percentage of participants |
| Kras Mutant Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 9.0 Percentage of participants |
| EGFR Mutant Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 44.4 Percentage of participants |
| EGFR Mutant Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 27.7 Percentage of participants |
| EGFR and Kras Wild Type Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 31.5 Percentage of participants |
| EGFR and Kras Wild Type Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 24.0 Percentage of participants |
| Patients With EML4-ALK Translocation | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 45.5 Percentage of participants |
| Patients With EML4-ALK Translocation | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 36.4 Percentage of participants |
| Modified EGFR Mutant Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 56.4 Percentage of participants |
| Modified EGFR Mutant Patients | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 37.8 Percentage of participants |
| Unknown | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 12 weeks | 33.3 Percentage of participants |
| Unknown | Progression Free Survival (PFS) Rate as Per Investigator Using Kaplan Meier Estimates - Per Investigator Radiological Review | 18 weeks | 33.3 Percentage of participants |