A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site

Summary

This study will compare the efficacy and safety of molecularly-guided therapy versus standard platinum-containing chemotherapy in participants with poor-prognosis cancer of unknown primary site (CUP; non-specific subset) who have achieved disease control after 3 cycles of first-line platinum based induction chemotherapy.

Timeline

Start

2018-07-10

Primary completion

2023-02-14

Completion

2024-11-07

Outcome

Met primary endpoint

registry Molecularly-Guided Therapy (MGT) Category 1 vs Chemotherapy Category 1; p = 0.0177; Stratified Cox proportional hazard 0.75 (95% CI 0.59 to 0.95); NCT03498521 ↗

paper 6·1 months (95% CI 4·7-6·5) in the MGT group versus 4·4 months (4·1-5·6) in the chemotherapy group (hazard ratio 0·72 [95% CI 0·56-0·92]; p=0·0079). PMID 39096924 ↗

Publications

• Kramer A, Bochtler T, Pauli C, Shiu KK, Cook N, de Menezes JJ, Pazo-Cid RA, Losa F, Robbrecht DG, Tomasek J, Arslan C, Ozguroglu M, Stahl M, Bigot F, Kim SY, Naito Y, Italiano A, Chalabi N, Duran-Pacheco G, Michaud C, Scarato J, Thomas M, Ross JS, Moch H, Mileshkin L. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet. 2024 Aug 10;404(10452):527-539. doi: 10.1016/S0140-6736(24)00814-6. Epub 2024 Jul 31.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Alectinib	Small molecule	600 mg	Oral
Subject	Atezolizumab	Monoclonal antibody	1200 mg	Intravenous
Subject	Bevacizumab	Monoclonal antibody	15 mg/kg	Intravenous
Comparator	Carboplatin	Small molecule	—	Intravenous
Comparator	Cisplatin	Other / unclassified	60 mg/m2	Intravenous
Comparator	Cisplatin	Other / unclassified	75 mg/m2	Intravenous
Subject	Cobimetinib	Small molecule	60 mg	Oral
Subject	Entrectinib	Small molecule	600 mg	Oral
Subject	Erlotinib	Small molecule	150 mg	Oral
Comparator	Gemcitabine	Small molecule	1000 mg/m2	Intravenous
Subject	Ipatasertib	Small molecule	400 mg	Oral
Subject	Ivosidenib	Small molecule	500 mg	Oral
Subject	Olaparib	Small molecule	400 mg	Oral
Subject	Paclitaxel	Small molecule	175 mg/m2	Intravenous
Subject	Pemigatinib	Small molecule	13.5 mg	Oral
Subject	Pertuzumab	Monoclonal antibody	420 mg	Intravenous
Subject	Trastuzumab	Monoclonal antibody	600 mg	Subcutaneous
Subject	Vemurafenib	Small molecule	960 mg	Oral
Subject	Vismodegib	Small molecule	150 mg	Oral

Indications