Virkestoff

Grunndose

Adm.måte

Oppløsningsvæske

Adm.tid

Beh.dager

Arm 1:

Pembrolizumab

200mg

iv

100ml NaCl 9 mg/ml

30 min

1

Arm 1:

Δ Lenvatinib *)

20 mg

po

Kapsel

Én gang daglig

1-21

Arm 3:

Δ Lenvatinib monoterapi *)

24 mg

po

Kapsel

Én gang daglig

Kontinuerlig

behandling

Treatment-Related Toxicity^a,b

Management

Dose Adjustment

Grade 1 or Tolerable Grade 2

Continue treatment

No change

Intolerable Grade 2^c,d and Grade 3^g

First occurrence

Interrupt lenvatinib until resolved to Grade 0-1, or tolerable Grade 2

Arm 3: Reduce lenvatinib dose to 20 mg once a day (1-level reduction)

Arm 1: Reduce lenvatinib dose to 14 mg once a day (1-level reduction)

Second occurrence
(same toxicity or new toxicity)

Interrupt lenvatinib until resolved to Grade 0-1, or tolerable Grade 2

Arm 3: Reduce lenvatinib dose to 14 mg once a day (1-level reduction)

Arm 1: Reduce lenvatinib dose to 10 mg once a day (1-level reduction)

Third occurrence
(same toxicity or new toxicity)

Interrupt lenvatinib until resolved to Grade 0-1, or tolerable Grade 2

Arm 3: Reduce lenvatinib dose to 10 mg once a day (1-level reduction)

Arm 1: Reduce lenvatinib dose to 8 mg once a day (1-level reduction)

Fourth occurrence
(same toxicity or new toxicity)

Interrupt lenvatinib

Discuss with sponsor

Grade 4^e,g: Discontinue study treatment

a. An interruption of study treatment for more than 28 days will require Sponsor approval before treatment can be resumed.

b. Initiate optimal medical management for nausea, vomiting, hypertension, hypothyroidism and/or diarrhea prior to any lenvatinib interruption or dose reduction.

c. Applicable only to Grade 2 toxicities judged by the participant and/or physician to be intolerable.

d. Obese participants (BMI ≥30) with weight loss do not need to return to their baseline weight or within 10% of their baseline weight (ie, Grade 1 weight loss). These participants may restart study intervention at a lower dose once their weight remains stable for at least 1 week and they have a minimum BMI of 25. The new stable weight should be used as the new baseline for further dose reductions.

e. For asymptomatic laboratory abnormalities, such as Grade ≥3 elevations of amylase and lipase that are not considered clinically relevant by the investigator, continuation of treatment should be discussed with Sponsor.

f. Excluding laboratory abnormalities judged to be non-life-threatening, in which case manage as Grade 3.

g. For Grade 3 thromboembolic event, permanently discontinue lenvatinib. See Section 6.6.2.5.