Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Etirinotecan pegol

Enzyme Inhibitors

NKTR-102 was administered as an intravenous (IV) infusion over 90 ± 10 minutes, on Day 1 of each 2-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 4 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

NKTR-102 was administered as an IV infusion over 90 ± 10 minutes, on Day 1 of each 3-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 6 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

NKTR-102 q14d

NKTR-102 q21d

Study Director

This is a multicenter, open-label, two-arm, 2-stage, Phase 2 study of NKTR-102 in patients with metastatic or locally advanced platinum-resistant ovarian cancer.

Approximately 70 patients will be randomized 1:1 into one of two treatment arms. NKTR-102 will be administered at a dose level of 145 mg/m\^2 in both arms. In Arm A, NKTR-102 will be given on a q14d schedule. In Arm B, NKTR-102 will be given on a q21d schedule. After the initial 70 patients have been enrolled, Arm B will enroll approximately 110 additional patients.

Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Ovarian Cancer

A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 When Given on a Q14 Day or a Q21 Day Schedule in Patients With Metastatic or Locally Advanced Platinum-Resistant Ovarian Cancer

The ORR was defined as the proportion of patients with a complete response (CR) or a partial response (PR) per RECIST 1.0 based upon the best response as assessed by the Investigator. CR was defined by RECIST 1.1 as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm. PR was defined by RECIST 1.1 as at least a 30% decrease in the sum of the diameters (SOD) of target lesions, taking as reference the baseline SOD. The analysis was performed for patients in the Primary Efficacy Population.

Best overall response was defined as the proportion of patients with a CR or a PR as assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and cancer antigen 125 (CA-125) criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the upper limit of normal (ULN) and within 2 weeks prior to starting treatment." Analysis was performed in MITT Population.

Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment." Analysis was performed in Primary Efficacy Population.

Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment." Analysis was performed in Platinum-Refractory Population.

Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. "A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment." Analysis was performed in Prior PLD Therapy Population.

According to enhanced RECIST 1.1, progressive disease was the appearance of one or more new lesions, OR an unambiguous increase in the sum of target lesion volumes with both 1) \>20% increase in the sum of volumes (SOV) of all target lesions (taking as reference the nadir) and 2) greater than two times the variability of the measurements estimated by the sponsor and/or its designees.

PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Primary Efficacy Population.

PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Platinum-Refractory Population.

PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Prior PLD Population.

DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in MITT Population.

DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Primary Efficacy Population.

DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Platinum-Refractory Population.

DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Prior PLD Therapy Population.

CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in MITT Population.

CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Primary Efficacy Population.

CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Platinum-Refractory Population.

CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Prior PLD Therapy Population.

Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in MITT Population.

Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Primary Efficacy Population.

Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Platinum-Refractory Population.

Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Prior PLD Therapy Population.

Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in MITT Population.

Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Primary Efficacy Population.

Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Platinum-Refractory Population.

Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Prior PLD Therapy Population.

The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the MITT Population.

The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the PLD Population.

The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the Platinum-Refractory Population.

Nektar Therapeutics

Safety Population=177 patients (n=38 NKTR-102 dose every 14 days; n=139 NKTR-102 dose every 21 days). All 177 participants experienced at least one adverse event, and 101 of them experienced at least one serious adverse event. Other Adverse Events section lists events occurring \> 5% of patients.

NKTR-102 was administered as an intravenous (IV) infusion over 90 ± 10 minutes, on Day 1 of each 2-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 4 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

Note: NKTR-102 was administered at a dose level of 170 mg/m2 (10 patients enrolled and received this dose for 1 to 3 cycles) until the dose was reduced to 145 mg/m2 for all ongoing patients in the q14d and q21d treatment schedules and this became the starting dose for all newly enrolled patients. The dose was reduced based on safety results from ongoing NKTR-102 Phase 1 and 2 clinical studies and the reduction was initiated with a waiver for study sites.

NKTR-102 was administered as an IV infusion over 90 ± 10 minutes, on Day 1 of each 3-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 6 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

Note: NKTR-102 was administered at a dose level of 170 mg/m2 (10 patients enrolled and received this dose for 1 to 3 cycles) until the dose was reduced to 145 mg/m2 for all ongoing patients in the q14d and q21d treatment schedules and this became the starting dose for all newly enrolled patients. The dose was reduced based on safety results from ongoing NKTR-102 Phase 1 and 2 clinical studies and the reduction was initiated with a waiver for study sites.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

The primary efficacy population consisted of patients in the modified intent-to-treat population (MITT) treated in q21d treatment schedule with platinum-resistant ovarian cancer who had received prior pegylated liposomal doxorubicin (PLD) therapy in a platinum-resistant setting or were otherwise unable to receive further PLD therapy.

Primary Efficacy Population

Received at least one dose of study treatment

Primary: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST): Primary Efficacy Population

The modified intent-to-treat (MITT) Population for the q14d Arm included all platinum-resistant ovarian cancer patients who were enrolled to the q14d treatment regimen. The MITT Population for the q21d Arm included all platinum-resistant ovarian cancer patients who were enrolled to the q21d treatment regimen. The MITT Population included those patients who had undergone radiographic tumor measurement evaluation at Baseline with measurable tumors, and were enrolled and received at least one dose (or partial dose) of study drug. Platinum-resistant patients had a platinum-free interval (PFI) ≤ 6 months. PFI was defined as the time to recurrence/progression from last dose of the prior platinum-based therapy.

MITT Population

Secondary: Best Overall Response by Gynecologic Cancer Intergroup (GCIG) Criteria: MITT Population

Patients in the MITT Population treated in q21d treatment schedule with platinum-resistant ovarian cancer, had received prior PLD therapy in a platinum-resistant setting or who were otherwise unable to receive further PLD therapy.

Secondary: Best Overall Response by GCIG Criteria: Primary Efficacy Population

Patients in the MITT Population with a PFI ≤ 6 weeks.

Platinum-Refractory Population

Secondary: Best Overall Response by GCIG Criteria: Platinum-Refractory Population

Patients in the MITT Population treated in q14d and q21d treatment schedules, who subsequently progressed after receiving PLD therapy or who were otherwise unable to receive PLD therapy.

Prior PLD Population

Secondary: Best Overall Response by GCIG Criteria: Prior PLD Therapy Population

Secondary: Kaplan-Meier Estimate of Progression-Free Survival (PFS): MITT Population

NKTR-102 was administered as an IV infusion over 90 ± 10 minutes, on Day 1 of each 3-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 6 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

Note: NKTR-102 was administered at a dose level of 170 mg/m2 (10 patients enrolled and received this dose for 1 to 3 cycles) until the dose was reduced to 145 mg/m2 for all ongoing patients in the q14d and q21d treatment schedules and this became the starting dose for all newly enrolled patients. The dose was reduced based on safety results from ongoing NKTR-102 Phase 1 and 2 clinical studies and the reduction was initiated with a waiver for study sites..

Secondary: Kaplan-Meier Estimate of PFS: Primary Efficacy Population

Secondary: Kaplan-Meier Estimate of PFS: Platinum-Refractory Population

Secondary: Kaplan-Meier Estimate of PFS: Prior PLD Therapy Population

Secondary: Kaplan-Meier Analysis of Duration of Overall Response (DoR): MITT Population

The primary efficacy population consisted of patients with platinum-resistant ovarian cancer in the modified intent-to-treat population (MITT) treated in q21d treatment schedule who had received prior pegylated liposomal doxorubicin (PLD) therapy in a platinum-resistant setting or were otherwise unable to receive further PLD therapy.

Secondary: Kaplan-Meier Analysis of DoR: Primary Efficacy Population

Secondary: Kaplan-Meier Analysis of DoR: Platinum-Refractory Population

Secondary: Kaplan-Meier Analysis of DoR: Prior PLD Therapy Population

Secondary: CA-125 Response Rate: MITT Population

The primary efficacy population only included subjects treated in the NKTR-102 q21d treatment arm.

Secondary: CA-125 Response Rate: Primary Efficacy Population

Secondary: CA-125 Response Rate: Platinum-Refractory Population

Secondary: CA-125 Response Rate: Prior PLD Therapy Population

Secondary: Clinical Benefit Rate: MITT Population

Secondary: Clinical Benefit Rate: Primary Efficacy Population

Secondary: Clinical Benefit Rate: Platinum-Refractory Population

Secondary: Clinical Benefit Rate: Prior PLD Therapy Population

Secondary: Kaplan-Meier Analysis of Overall Survival (OS): MITT Population

Secondary: Kaplan-Meier Analysis of OS: Primary Efficacy Population

Secondary: Kaplan-Meier Analysis of OS: Platinum-Refractory Population

Secondary: Kaplan-Meier Analysis of OS: Prior PLD Therapy Population

Secondary: ORR by RECIST: MITT Population

Secondary: ORR by RECIST: Prior PLD Population

NKTR-102 was administered as an intravenous (IV) infusion over 90 ± 10 minutes, on Day 1 of each 2-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 4 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

Note: NKTR-102 was administered at a dose level of 170 mg/m2 (10 patients enrolled and received this dose for 1 to 3 cycles) until the dose was reduced to 145 mg/m2 for all ongoing patients in the q14d and q21d treatment schedules and this became the starting dose for all newly enrolled patients. The dose was reduced based on safety results from ongoing NKTR-102 Phase 1 and 2 clinical studies and the reduction was initiated with a waiver for study sites and shortly thereafter included in Protocol Amendment 1.0 dated 26 Mar 2009.

NKTR-102 was administered as an IV infusion over 90 ± 10 minutes, on Day 1 of each 3-week \[± 2 days\] cycle at a dose of 170 mg/m\^2 for the first 6 patients enrolled and at a dose of 145 mg/m\^2 for the remainder of the patients.

Note: NKTR-102 was administered at a dose level of 170 mg/m2 (10 patients enrolled and received this dose for 1 to 3 cycles) until the dose was reduced to 145 mg/m2 for all ongoing patients in the q14d and q21d treatment schedules and this became the starting dose for all newly enrolled patients. The dose was reduced based on safety results from ongoing NKTR-102 Phase 1 and 2 clinical studies and the reduction was initiated with a waiver for study sites and shortly thereafter included in Protocol Amendment 1.0 dated 26 Mar 2009.

Spots Global Cancer Trial Database for Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Ovarian Cancer

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