Phase 2
Completed N=540
Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Participants With Advanced Melanoma (MK-3475-002/P08719/KEYNOTE-002)
Source: ClinicalTrials.gov NCT01704287 ↗Enrolled (actual)
540
Serious AEs
41.9%
Results posted
Mar 2017
Primary outcomePrimary: Progression-free Survival (PFS) - Initial Treatment Period — 2.9; 3.0; 2.8 Months — p=<0.0001
Summary
This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL) who had progressed after prior therapy.
Initial Treatment Period:
Participants were initially randomized to receive either low-dose (2 mg/kg) pembrolizumab, higher dose (10 mg/kg) pembrolizumab or Investigator-choice chemotherapy (ICC). The four standard chemotherapy choices were: carboplatin + paclitaxel, paclitaxel alone, dacarbazine, or temozolomide. The randomization to either pembrolizumab or ICC was conducted in an open-label fashion.
The starting pembrolizumab dose was initially blinded to Investigators and participants until Amendment 03. With Amendment 03, all ongoing pembrolizumab participants were to be treated with open label, fixed dose pembrolizumab 200 mg, instead of a weight-based dosing of pembrolizumab.
Switch-to-Pembrolizumab Treatment Period:
Participants who were initially randomized to receive ICC and experienced progressive disease (PD) may have been eligible to switch to receiving pembrolizumab provided they met protocol-specified requirements for switching. Qualified participants were re-randomized to receive either pembrolizumab 2 mg/kg or pembrolizumab 10 mg/kg in a double-blind fashion. Participants who qualified to switch to pembrolizumab must have completed a washout period of ≥28 days from last dose of chemotherapy before receiving pembrolizumab. With Amendment 03, all switched-to-pembrolizumab participants were to be treated with open-label, fixed dose pembrolizumab 200 mg instead of a weight-based dosing of pembrolizumab.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) - Initial Treatment Period |
2.9; 3.0; 2.8 | <0.0001 sig |
| PRIMARY Interim Overall Survival (OS) - Initial Treatment Period |
13.4; 14.7; 11.0 | 0.1173 |
| PRIMARY Final Overall Survival (OS) - Initial Treatment Period |
13.4; 14.7; 11.0 | 0.1146 |
| SECONDARY Final Overall Survival (OS) By Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Status - Initial Treatment Period |
15.0; 17.5; 12.1; 10.5; 13.4; 9.3 | 0.3113 |
| SECONDARY Overall Response Rate (ORR) - Initial Treatment Period |
22.2; 27.6; 4.5 | — |
| SECONDARY Best Overall Response (BOR) - Initial Treatment Period |
3.3; 7.2; 0.0; 18.9; 20.4; 4.5 | — |
| SECONDARY Best Overall Response (BOR) - Switch-to-Pembrolizumab Treatment Period |
1.9; 4.4; 17.0; 13.3; 15.1; 11.1 | — |
| SECONDARY Duration of Response (DOR) - Initial Treatment Period |
22.8; NA; 6.8 | — |
| SECONDARY Number of Participants Who Experienced an Adverse Event (AE) - Overall Study |
172; 179; 71; 52; 45; 53 | — |
| SECONDARY Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) - Overall Study |
29; 33; 13; 1; 1; 4 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic MEL not amenable to local therapy
- Participants must be refractory to ipilimumab
- Participants with BRAF gene mutant melanoma must have had a prior treatment regimen that included vemurafenib, dabrafenib, or an approved BRAF gene and/or mitogen-activated protein kinase (MEK) protein inhibitor
- Must consent to allow correlative studies; must provide a newly obtained tissue/biopsy specimen (or specimen obtained within 60 days of consenting)
- Radiographically measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria
- Chemotherapy, radiation therapy, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or not recovered from the AEs due to cancer therapies administered more than 4 weeks earlier
- Disease progression within 24 weeks of last dose of ipilimumab
- Participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug
- Expected to require any other form of systemic or localized antineoplastic therapy while on study
- Chronic systemic steroid therapy within 2 weeks before the planned date for first dose randomized treatment or on any other form of immunosuppressive medication
- Known history of any other than the current malignancy excepting adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, breast cancer, or other in situ cancers
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Active autoimmune disease or a history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents
- Prior treatment with any other anti-programmed cell death (PD) agent
- Active infection requiring systemic therapy
- Known history of Human Immunodeficiency Virus (HIV)
- Active Hepatitis B or Hepatitis C
- Regular user (including recreational use of) illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study through 120 days after last dose of study drug
Data sourced from ClinicalTrials.gov (NCT01704287). 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.