Phase 2
Completed N=240
Safety and Efficacy Study of Nab®-Paclitaxel With CC-486 or Nab®-Paclitaxel With Durvalumab, and Nab®-Paclitaxel Monotherapy as Second/Third-line Treatment for Advanced Non-small Cell Lung Cancer
Source: ClinicalTrials.gov NCT02250326 ↗Enrolled (actual)
240
Serious AEs
44.1%
Results posted
Aug 2018
Primary outcomePrimary: Kaplan Meier Estimate of Progression-Free Survival (PFS) as Assessed by the Investigator — 3.2; 4.5; 4.2 months
Summary
This is a Phase 2, open-label, multicenter study to assess the efficacy and safety of second/third-line treatment with nab-paclitaxel in combination with the epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab, and nab-paclitaxel monotherapy in subjects with advanced non-small cell lung cancer (NSCLC).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Kaplan Meier Estimate of Progression-Free Survival (PFS) as Assessed by the Investigator |
3.2; 4.5; 4.2 | — |
| SECONDARY Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) According to RECIST V 1.1 Criteria |
65.4; 70.9; 67.5 | — |
| SECONDARY Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST V 1.1 Criteria |
13.6; 27.8; 16.3 | — |
| SECONDARY Kaplan Meier Estimate of Overall Survival (OS) |
8.1; 10.1; 17.0 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Entire Treatment Period |
79; 78; 78; 30; 44; 30 | — |
| SECONDARY Percentage of Participants Who Discontinued Study Treatment |
100.0; 100.0; 100.0 | — |
| SECONDARY Dose Intensity Per Week of Nab-Paclitaxel |
54.73; 57.18; 58.61 | — |
| SECONDARY Dose Intensity Per Week of CC-486 |
716.66 | — |
| SECONDARY Dose Intensity Per Week of Durvalumab |
279.96 | — |
| SECONDARY Percentage of Participants With Study Drug Dose Reductions |
10.1; 14.1; 10.1; 20.3; 0.0 | — |
Eligibility Criteria
Inclusion Criteria: 1.Age ≥ 18 years the time of signing the Informed Consent Form (ICF).
- Understand and voluntarily provide written informed consent prior to the conduct of any study related assessments/procedures.
- Able to adhere to the study visit schedule and other protocol requirements. 4. Histologically or cytologically confirmed advanced NSCLC who will receive study therapy as second- or third-line of treatment for advanced disease.
- No other current active malignancy requiring anticancer therapy. 6. Radiographically documented measurable disease (defined by the presence of ≥ 1 radiographically documented measurable lesion).
- One prior platinum-containing chemotherapy for metastatic or recurrent NSCLC unless patients are ineligible to receive it. Patients may have received no more than one line of chemotherapy; immunotherapy in prior line of treatment (first or second line) is allowed. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
- Platelets ≥ 100, 000 cells/mm3. 9. Hemoglobin (Hgb) ≥ 9 g/dL. 10. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
- Total bilirubin ≤ 1.5 ULN (unless there is a known history of Gilberts Syndrome).
- Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance ≥ 60 mL/min (if renal impairment is suspected 24-hour urine collection for measurement is required).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 15. Females of childbearing potential [defined as a sexually mature woman who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months)] must:
- Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 hours prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.
- Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 3 months after discontinuation of study therapy.
Male subjects must:
- Practice true abstinence* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following IP discontinuation, even if he has undergone a successful vasectomy.
- Refrain from semen or sperm donation while taking durvalumab and for at least 3 months after the last dose of durvalumab.
- Females must abstain from breastfeeding during study participation and 3 months after IP discontinuation.
Exclusion Criteria
- The presence of any of the following will exclude a subject from enrollment:
- Refractory to prior taxane therapy for advanced disease. Prior taxane used in the adjuvant setting does not exclude eligibility, provided there is no disease recurrence within 12 months upon completion of chemotherapy in that setting.
- Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if asymptomatic and clinically stable for at least 8 weeks following completion of therapy). MRI of the brain (or CT scan w/contrast) is preferred.
- Only evidence of disease is non-measurable at study entry.
- Known activating E
Data sourced from ClinicalTrials.gov (NCT02250326). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.