Melanoma: KEYNOTE-006 trial

Abbreviations

No EU-CTR

Investigated (inv)
Comparator (comp)

PEMB q3w

IPIL q3w

277

278

Phase:

3

Randomisation:

Open label

Primary tumour:

Melanoma

Subtype (biomarker):

Any

Stage:

meta

Line of therapy:

L1

Primary
PEMB q3w
IPIL q3w
HR
p
PFS @6mo
46.4%
26.5%
0.58 (0.47-0.72)
<0.001
OS @1yr
68.4%
58.2%
0.69 (0.52-0.90)
0.0036
Secondaries
PEMB q3w
IPIL q3w
HR
p
ORR
32.9%
11.9%
<0.001
DoR @7.9mo
96.7%
87.9%
Time to response
85 d
87 d
(all grades, %)
PEMB q3w
IPIL q3w
p
Fatigue
19.1
15.2
NA
Diarrhea
14.4
22.7
NA
Rash
13.4
14.5
NA
Vitiligo
11.2
1.6
NA
Hypothyroidism
8.7
2.0
NA
Hyperthyroidism
3.2
2.3
NA
Colitis
3.6
8.2
NA
Hepatitis
1.8
1.2
NA
Hypophysitis
0.7
2.3
NA
Pneumonitis
1.8
0.4
NA
Nausea
11.2
8.6
NA
Arthralgia
11.6
5.1
NA
Uveitis
1.1
0.0
NA
Nephritis
0.4
0.4
NA
  • Inclusion
  • Exclusion

- Histologically-confirmed diagnosis of unresectable Stage III or metastatic melanoma not amenable to local therapy (excluding uveal or ocular melanoma) - At least one measurable lesion - No prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (first line) or one prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (second line) - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Archived tissue sample or new biopsy sample - Female participants of childbearing potential must agree to use effective contraception from Visit 1 to 120 days after the last dose of study drug; male participants must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug.

- Prior treatment with ipilimumab or other anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) agent or any anti-programmed cell death (PD-1 or PD-L2) agent - Chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of study drug, or not recovered from adverse events caused by cancer therapeutics administered more than four weeks earlier - Currently 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 - On any systemic steroid therapy within one week before the planned date for first dose of randomized treatment or on any other form of immunosuppressive medication - History of a malignancy (other than the disease under treatment in the study) within 5 years prior to first study drug administration, excluding adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other in situ cancers. - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases are eligible - Severe hypersensitivity reaction to treatment with another monoclonal antibody - Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents - Active infection requiring systemic therapy - Known history of Human Immunodeficiency Virus (HIV) - Known history of or positive for Hepatitis B or C - Known psychiatric or substance abuse disorder - 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 - Received a live vaccine within 30 days prior to first dose of study drug.

Characteristics
PEMB q3w
IPIL q3w
Agedc-comma sex
Median age (range)dc-comma yr
63 (22–89)
62 (18–88)
Male
62.8%
58.3%
ECOG
0
68.2%
67.6%
1
31.8%
32.4%
Metastasis stage - no.(%)
M0
9 (3.2)
14 (5.0)
M1a
34 (12.3)
30 (10.8)
M1b
41 (14.8)
52 (18.7)
M1c
189 (68.2)
177 (63.7)
Line of previous systemic therapy - no.(%)
0
185 (66.8)
181 (65.1)
1
91 (32.9)
97 (34.9)
Type of previous systemic therapy - no.(%)
Chemotherapy
41 (14.8)
29 (10.4)
Immunotherapy
7 (2.5)
12 (4.3)
BRAF or MEK inhibitor or both
45 (16.2)
56 (20.1)
Other
Elevated baseline LDH level - no.(%)
98 (35.4)
91 (32.7)
PD-L1–positive tumor - no.(%)
221 (79.8)
225 (80.9)
BRAF V600 mutation - no.(%)
97 (35.0)
107 (38.5)
Brain metastasis - no.(%)
27 (9.7)
28 (10.1)
Ad-hoc:
no.pts inv.
no.pts comp.
PEMB q3w
IPIL q3w
HR
p
  • PFS @6mo
  • OS @1yr
analisys of PFS @6mo
PEMB q3w
IPIL q3w
HR (95% CI)
Age
<65 yr
0.59 (0.45-0.79)
≥65 yr
0.57 (0.41-0.81)
Sex
Male
0.57 (0.42-0.77)
Female
0.59 (0.43-0.83)
Racedc-comma region
White race
0.58 (0.47-0.72)
Other than US
0.60 (0.48-0.76)
ECOG
0 (n=337)
0.62 (0.48-0.81)
1 (n=178)
0.53 (0.36-0.73)
PD-L1 status
Positive (n=446)
0.52 (0.40-0.66)
Negative (n=101)
0.76 (0.47-1.24)
BRAF status
Wild type
0.57 (0.43-0.75)
Mutantdc-comma no anti-BRAF
0.44 (0.26-0.75)
No previous imunotherapy
PEMB q2w vs IPIL q3w
0.58 (0.46-0.72)
PEMB q3w vs IPIL q3w
0.57 (0.46-0.72)
Line of therapy
First
0.50 (0.38-0.66)
Second
0.80 (0.56-1.14)
analisys of OS @1yr
PEMB q3w
IPIL q3w
HR (95% CI)
Age
<65 yr
0.77 (0.53-1.12)
≥65 yr
0.66 (0.44-1.01)
Sex
Male
0.66 (0.45-0.95)
Female
0.78 (0.51-1.21)
Racedc-comma region
White race
0.69 (0.52-0.91)
Other than US
0.65 (0.49-0.88)
ECOG
0
0.75 (0.52-1.07)
1
0.60 (0.39-0.94)
PD-L1 status
Positive
0.58 (0.42-0.79)
Negative
1.02 (0.56-1.85)
BRAF status
Wild type
0.66 (0.47-0.92)
Mutantdc-comma no anti-BRAF
0.71 (0.30-1.67)
No previous imunotherapy
PEMB q2w vs IPIL q3w
0.62 (0.47-0.83)
PEMB q3w vs IPIL q3w
0.67 (0.50-0.88)
Line of therapy
First
0.68 (0.47-0.96)
Second
0.69 (0.44-1.09)