| ALK fusion |
ALEX[@99671; @99672] |
III |
ALK inhibitor naiive |
Alectinib 600 mg BID vs. crizotinib 250 mg BID |
303 |
82.9% (76.0–88.5) vs. 75.5% (67.8–82.1), p=0.09 |
34.8 (17.7-NE) vs. 10.9 (9.1–12.9), HR 0.43 (0.32–0.58), p < 0.0001 |
NR vs. 57.4 (34.6-NR), HR 0.67 (0.46–0.98) |
|
ALTA-1L[@99673; @99674] |
III |
ALK inhibitor naiive |
Brigatinib 180 mg daily vs. crizotinib 250 mg BID |
275 |
74% (66-81) vs. 62% (53-70), OR 1.73 (1.04-2.88), p=0.0342 |
24.0 (18.5-NR) vs. 11 (9.2–12.9), HR 0.49 (0.35–0.68), p < 0.0001 |
HR 0.92 (0.57–1.47), p = 0.771 |
|
CROWN[@99675] |
III |
First |
Lorlatinib 100 mg daily vs. crizotinib 250 mg BID |
296 |
76% (68–83) vs. 58% (49–66), OR 2.25 (1.35-3.89) |
NR (NR-NR) vs. 9.3 (7.6–11.1), HR 0.28 (0.19–0.41), p < 0.001 |
HR 0.72 (0.41–1.25) |
| ROS1 fusion |
ALKA-372-001, STARTRK-1, STARTRK-2[@99676] |
I/II |
ROS1 inhibitor naiive |
Entrectinib ≥600 mg daily |
161 |
67.1% (59.3-74.3) |
15.7 (11.0-21.1) |
|
|
PROFILE 1001[@99677; @99678] |
I |
ROS1 inhibitor naiive |
Crizotinib 250 mg BID |
53 |
72% (58-83) |
19.3 (15.2-39.1) |
51.4 (29.3-NR) |
|
Lim et al.[@99679] |
II |
ROS1 inhibitor naiive (except 2) |
Ceritinib 750 mg daily |
32 |
62% (45-77) |
9.3 (0-22) |
24 (5-43) |
| BRAF V600E |
Planchard et al.[@99680] |
II |
First |
Dabrafenib 150 mg BID and trametinib 2 mg daily |
36 |
64% (46-79) |
14.6 (7.0-22.1) |
24.6 (12.3-NE) |
| KRAS G12C |
CodeBreaK100[@99681; @99682] |
II |
Patients progressed following immunotherapy and/or platinum-based therapy |
Sotorasib 960 mg daily |
126 |
37.1% (28.6-46.2) |
6.8 (5.1-8.2) |
12.5 (10.0-NE) |
| NTRK1/2/3 fusion |
NAVIGATE and NCT02122913[@99683; @99684] |
I/II |
Heavily pretreated |
Larotrectinib 100 mg BID |
20 |
73% (45-92) |
|
40.7 (17.2-NE) |
|
ALKA-372-001, STARTRK-1, STARTRK-2[@99683; @99685] |
I/II |
TRK-inhibitor naïve |
Entrectinib, varying doses |
10 with NSCLC |
70% (35-93) |
|
21 (14.9-NE) for all 54 patients |
| RET fusion |
LIBRETTO[@99686] |
I/II |
First and post-platinum treatment |
Selpercatinib 160 mg BID |
39 treatment naïve and 105 platinum-treated |
85% (70-94) in treatment naïve and 64% (54-73) in platinum-treated |
16.5 (13.7-NE) in platinum-treated patients |
|
|
ARROW[@99687] |
I/II |
First and post-platinum treatment |
Pralsetinib 400 mg daily |
27 treatment naïve and 87 platnum-treated |
70% (50-86) in treatment naïve and 61% (50-71) in platinum-treated |
9.1 (6.1-13.0) in treatment naïve and 17.1 (12.7-18.4) in platinum-treated |
|
| MET exon 14 skipping |
GEOMETRY[@99688] |
II |
Various |
Capmatinib 400 mg BID |
28 treatment naïve and 69 who had received one or two lines of prior therapy |
68% (48-84) in treatment naïve and 41% (29-53) in patients with one or two prior lines of therapy |
12.4 (8.2-NE) in treatment naïve and 5.4 (4.2-7.0) in patients with prior treatment |
|
|
VISION[@99689] |
II |
Previous treatment with up to two courses |
Tepotinib 500 mg daily |
99 |
46% (36-57) |
8.5 (6.7-11.0) |
17.1 (12.0-26.8) |