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Paclitaxel

Albumin-Bound Paclitaxel

Abraxane (nab®paclitaxel) 125 milligrams per meter squared on days 1, 8 and 15 of a 28 day cycle

ABI-007

Alfredo Romano, MD

The purpose of this study is to evaluate the safety and efficacy of Abraxane (nab-paclitaxel) in subjects with previously treated metastatic colorectal cancer. Subjects will be placed into two separate cohorts based on their RAS mutation status.

ABI-007-COLO-001 is a Phase 2, single arm, open label, multicenter study to evaluate the efficacy and safety of Abraxane (nab-paclitaxel) given on days 1, 8 and 15 of a 28 day cycle in subjects with previously treated metastatic colorectal cancer. Subjects will be enrolled into cohorts by RAS mutation status (wildtype or mutated). Stage 1 in a given cohort will enroll 15 subjects in the Intention to Treat population and if more than 8 subjects have Progression Free Survival at the 8 week assessment, then Stage 2 will open in the respective cohort. Stage 2 will enroll an additional 28 subjects for a total of 43 subjects in each cohort. The study will be positive if more than 26 subjects with Progression Free Survival at the 8 week assessment are observed in 43 subjects per cohort. Interim analysis after Stage 1 did not meet protocol defined criteria to proceed to Stage 2. Patients currently enrolled will be followed for Progression Free Survival and until 28 days after last dose, secondary endpoints including overall survival will not be followed

Phase 2 Study With Abraxane (Nab®Paclitaxel) in Metastatic Colorectal Cancer

A SINGLE ARM PHASE 2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF Nab®-PACLITAXEL, IN SUBJECTS WITH PREVIOUSLY TREATED METASTATIC COLORECTAL CANCER

PFS was measured as time from the date of first dose to the date of disease progression according to RECIST 1.1 or death from any cause, whichever was earlier.

PFS rate was measured by Investigator Assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 from the start of study treatment to disease progression or death from any cause, whichever occurred first.

DCR was defined as the combined incidence of stable disease confirmed CR or PR and stable disease (SD) measured at the Week 8 assessment or later.

Overall Survival was the time from the first dose of study drug to patient death from any cause.

ORR was defined as the combined incidence of Complete Response (CR) and Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met based on RECIST 1.1. Tumor responses were assessed every 2 cycles using RECIST 1.1 and defined as: • Complete response-disappearance of all target lesions • Partial response- At least a 30% decrease in the sum of diameters of target lesions from baseline • Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD) • Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

Duration of response was defined as the time from the first tumor assessment when the confirmed CR/PR response criterion was met to the date of disease progression based on investigational assessment following RECIST 1.1.

A treatment emergent adverse events (TEAE) was defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. A TESAE is defined as any serious adverse event (SAE) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. Safety and Severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Lifethreatening; Grade 5-Fatal;

Celgene

nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.

RAS Wildtype: Nab®-Paclitaxel

RAS Mutated: Nab®-Paclitaxel

Total

Age, Continuous

Sex: Female, Male

Intent to Treat (ITT) Includes participants who met all eligibility criteria and received at least one dose of study drug.

Anne McClain, Senior Manager, Clinical Trial Disclosure

Per the Simon 2-stage design, only 30 participants from Stage 1 (the first 15 participants in the Intent to Treat (ITT) population from each cohort) were included. The ITT population was defined as those who received treatment and met all eligibility criteria; four ineligible participants were excluded based on the protocol deviations/violations

Progression Free Survival (PFS) Rate as Measured at Week 8

ITT Population defined as participants who received treatment and met all eligibility criteria

Percentage of Participants With Stable Disease for ≥ 8 Weeks, or Complete or Partial Response According to RECIST Version 1.1; Disease Control Rate (DCR)

The data from the primary efficacy endpoint met the stopping criteria defined by the Simon 2-stage design, which did not support further assessment of nab-paclitaxel as a monotherapy in the analysis of this group of participants. The study was stopped early and the analysis of overall survival was not performed.

Overall Survival

ITT population defined as participants who received treatment and met all eligibility criteria.

Overall Response Rate (ORR)

Abraxane (nab®-paclitaxel) 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.

RAS Wildtype Abraxane (Nab®-Paclitaxel)

RAS Mutated Abraxane (Nab®-Paclitaxel)

The data from the primary efficacy endpoint met the stopping criteria defined by the Simon 2-stage design, which did not support further assessment of nab-paclitaxel as a monotherapy in the analysis of this group of participants. Duration of response was not analyzed as there were no responders observed in the study.

Duration of Response (DOR)

Any TEAE

≥1 or more related TEAE

≥1 TEAE with Grade 3-4

≥1 treatment related TEAE with Grade 3 or 4

≥1 or TEAE Grade 3 or higher

≥1 treatment related TEAE with Grade 3 or higher

Any Serious TEAE

≥1 or more related serious TEAE

≥1TEAE with Action of Study Drug Withdrawn

≥1treatment related TEAE WhereStudy Drug Withdrawn

≥1TEAE with Action of Study Drug Reduced

≥1 treatment related TEAE Where Study Drug Reduced

≥1TEAE with study dose Interrupted

≥1 treatment related TEAE w Study Drug Interrupted

≥1TEAE with outcome of death

Safety population includes all participants who received at least one dose of study treatment

Number of Participants With Adverse Events

Intent-to-treat Population defined as participants who received treatment and met all eligibility criteria

Spots Global Cancer Trial Database for nab®paclitaxel