Table 3. Clinical studies of... | American Society of Hematology

Table 3.

Clinical studies of RAS-pathway–targeted therapies

Retrospective cohorts and case reports
Type	Year published	Patient population	Combination/administration	No. of patients	ORR
Retrospective	2016⁷⁸	Oncogenic mutations of NRAS, KRAS, or BRAF or GEP pathway activation in relapsed/refractory patients	Trametinib (single agent or in combination with other agents)	58 (40 with measurable disease at time of commencing trametinib)	16/40 (40%)
Case report	2017⁸⁴	Relapsed/refractory patient with extramedullary disease and BRAF V600E mutation	Vemurafenib and cobimetinib	1	Patient responded
Case report	2014⁸⁵	Relapsed/refractory patient with extramedullary disease and BRAF V600E mutation	Vemurafenib	1	Patient progressed through treatment
Case report	2014⁸⁶	Relapsed/refractory patients with BRAF V600E mutations	Vemurafenib	2	Both patients responded
Case report	2013⁸⁷	Relapsed/refractory patient with extramedullary disease and BRAF V600E mutation	Vemurafenib	1	Patient responded

Retrospective cohorts and case reports
Type	Year published	Patient population	Combination/administration	No. of patients	ORR
Retrospective	2016⁷⁸	Oncogenic mutations of NRAS, KRAS, or BRAF or GEP pathway activation in relapsed/refractory patients	Trametinib (single agent or in combination with other agents)	58 (40 with measurable disease at time of commencing trametinib)	16/40 (40%)
Case report	2017⁸⁴	Relapsed/refractory patient with extramedullary disease and BRAF V600E mutation	Vemurafenib and cobimetinib	1	Patient responded
Case report	2014⁸⁵	Relapsed/refractory patient with extramedullary disease and BRAF V600E mutation	Vemurafenib	1	Patient progressed through treatment
Case report	2014⁸⁶	Relapsed/refractory patients with BRAF V600E mutations	Vemurafenib	2	Both patients responded
Case report	2013⁸⁷	Relapsed/refractory patient with extramedullary disease and BRAF V600E mutation	Vemurafenib	1	Patient responded

Ongoing studies
Phase	Location	Patient population	Combination/administration	NCT	Estimated completion
1	UK	Relapsed/refractory	RO5126766 twice weekly or Monday/Wednesday/Friday dosing schedule	NCT02407509	2016 (but ongoing)
1	UK	BRAF, NRAS, or KRAS mutated		NCT02407509	2016 (but ongoing)
1	US	Relapsed/refractory	Cohort 1: BRAF V600 mutated: dabrafenib; cohort 2 BRAF mutated or BRAF and KRAS/NRAS mutated: trametinib; cohort 3: KRAS or NRAS mutated: trametinib	NCT03091257	2021
1	US	BRAF, NRAS, or KRAS mutated		NCT03091257	2021
2	Canada	Relapsed/refractory BRAF, NRAS, or KRAS mutated	Trametinib initially with the AKT inhibitor GSK2141795 added at progression	NCT01989598	2018
2	Canada		Cohorts of biomarker-positive and negative patients	NCT01989598	2018
2	Germany	Relapsed/refractory	Encorafenib and binimetinib combination	NCT02834364	2021
2	Germany	BRAF V600E/K mutated	Encorafenib and binimetinib combination	NCT02834364	2021
1b/2	Europe	Relapsed/refractory	Arm A: cobimetinib; arm B: cobimetinib and venetoclax; arm C: cobimetinib, venetoclax, and atezolizumab	NCT03312530	2020
1b/2	Europe	3 to 5 prior lines of therapy		NCT03312530	2020

Ongoing studies
Phase	Location	Patient population	Combination/administration	NCT	Estimated completion
1	UK	Relapsed/refractory	RO5126766 twice weekly or Monday/Wednesday/Friday dosing schedule	NCT02407509	2016 (but ongoing)
1	UK	BRAF, NRAS, or KRAS mutated		NCT02407509	2016 (but ongoing)
1	US	Relapsed/refractory	Cohort 1: BRAF V600 mutated: dabrafenib; cohort 2 BRAF mutated or BRAF and KRAS/NRAS mutated: trametinib; cohort 3: KRAS or NRAS mutated: trametinib	NCT03091257	2021
1	US	BRAF, NRAS, or KRAS mutated		NCT03091257	2021
2	Canada	Relapsed/refractory BRAF, NRAS, or KRAS mutated	Trametinib initially with the AKT inhibitor GSK2141795 added at progression	NCT01989598	2018
2	Canada		Cohorts of biomarker-positive and negative patients	NCT01989598	2018
2	Germany	Relapsed/refractory	Encorafenib and binimetinib combination	NCT02834364	2021
2	Germany	BRAF V600E/K mutated	Encorafenib and binimetinib combination	NCT02834364	2021
1b/2	Europe	Relapsed/refractory	Arm A: cobimetinib; arm B: cobimetinib and venetoclax; arm C: cobimetinib, venetoclax, and atezolizumab	NCT03312530	2020
1b/2	Europe	3 to 5 prior lines of therapy		NCT03312530	2020

Umbrella/basket studies
Phase	Location	Patient population	Combination/administration	NCT	Estimated completion
2	US	MATCH study: multiple diseases and multiple treatments	Guided by molecular characterization, including BRAF, RAS, PIKC3A mutations, CCND1, CDK4, CDK6 amplification	NCT02465060	2022
2	US	TAPUR study: multiple diseases and multiple treatments	Guided by genomic variant identification, including BRAF, KRAS, NRAS	NCT02693535	2019
2	Canada	CAPTUR study: multiple diseases and multiple treatments	Guided by genomic variant identification, including BRAF	NCT03297606	2021

Umbrella/basket studies
Phase	Location	Patient population	Combination/administration	NCT	Estimated completion
2	US	MATCH study: multiple diseases and multiple treatments	Guided by molecular characterization, including BRAF, RAS, PIKC3A mutations, CCND1, CDK4, CDK6 amplification	NCT02465060	2022
2	US	TAPUR study: multiple diseases and multiple treatments	Guided by genomic variant identification, including BRAF, KRAS, NRAS	NCT02693535	2019
2	Canada	CAPTUR study: multiple diseases and multiple treatments	Guided by genomic variant identification, including BRAF	NCT03297606	2021

As per www.clinicaltrials.gov and PubMed searches for “myeloma” and the following terms: “vemurafenib,” “dabrafenib,” “trametinib,” “cobimetinib,” “RAS,” “BRAF,” and “MEK.”