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AzTrials

MelanomaPhase 3COMBI-iNCT02967692

A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma

A Phase 3 study testing Spartalizumab, Dabrafenib and Trametinib in people with Melanoma, run by Novartis Pharmaceuticals at 179 sites in 29 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study was to evaluate safety and efficacy of the combination of an anti-PD-1 antibody (PDR001), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in patients with BRAF V600 mutant, unresectable and metastatic melanoma. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Melanoma
What is being tested?
Spartalizumab, Dabrafenib and Trametinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
568 participants
Where
179 sitesin 29 countries
Study dates
17 Feb 2017to 21 Aug 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
  • Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN
  • Measurable disease according to RECIST 1.1
  • ECOG performance status ≤ 1
  • Part 2: Biomarker cohort
  • Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
Show all 13Show fewer
  • At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection
  • Measurable disease according to RECIST 1.1
  • ECOG performance status ≤ 2
  • Part 3: Double-blind, randomized, placebo-controlled part
  • Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
  • ECOG performance status ≤ 2
  • Measurable disease according to RECIST 1.1

Who cannot join

  • Part 1: Safety run-in
  • Subjects with uveal or mucosal melanoma
  • Any history of CNS metastases
  • Prior systemic anti-cancer treatment for unresectable or metastatic melanoma
  • Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollmen
  • Radiation therapy within 4 weeks prior to start of study treatment
Show all 15Show fewer
  • Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment
  • Parts 2 \& 3: Biomarker cohort \& double-blind, randomized, placebo-controlled part
  • Subjects with uveal or mucosal melanoma
  • Prior systemic anti-cancer treatment for unresectable or metastatic melanoma
  • Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollment
  • Radiation therapy within 4 weeks prior to start of study treatment
  • Clinically active cerebral melanoma metastasis.
  • Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment
  • Other protocol-defined Inclusion/Exclusion may apply.

Trial locations and contacts

179 sites in 29 countries.

179 sites in 29 countries

France26 sites

  • Novartis Investigative Site

    Amiens, 80054

  • Novartis Investigative Site

    Besançon, 25030

  • Novartis Investigative Site

    Bobigny, 93009

  • Novartis Investigative Site

    Bordeaux, 33075

  • Novartis Investigative Site

    Boulogne-Billancourt, 92104

  • Novartis Investigative Site

    Caen, 14033

  • Novartis Investigative Site

    Clermont-Ferrand, 63003

  • Novartis Investigative Site

    Dijon, 21034

  • Novartis Investigative Site

    Grenoble, 38043

  • Novartis Investigative Site

    Le Mans, 72000

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Limoges, Haute Vienne, 87000

  • Novartis Investigative Site

    Lorient, 56322

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Marseille, 13885

  • Novartis Investigative Site

    Mulhouse, 68070

  • Novartis Investigative Site

    Nice, 06202

  • Novartis Investigative Site

    Paris, 75475

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Poitiers, 86021

  • Novartis Investigative Site

    Reims, 51092

  • Novartis Investigative Site

    Rouen, 76031

  • Novartis Investigative Site

    Strasbourg, 67091

  • Novartis Investigative Site

    Toulouse, 31059

  • Novartis Investigative Site

    Vandœuvre-lès-Nancy, 54519

  • Novartis Investigative Site

    Villejuif, 94800

Other trials in France

Germany26 sites

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Berlin, 13578

  • Novartis Investigative Site

    Bonn, 53105

  • Novartis Investigative Site

    Chemnitz, 09117

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Düsseldorf, 40225

  • Novartis Investigative Site

    Erfurt, 99089

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Freiburg im Breisgau, 79106

  • Novartis Investigative Site

    Gera, 07548

  • Novartis Investigative Site

    Halle, Saxony-Anhalt, 06120

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Hanover, 30625

  • Novartis Investigative Site

    Heidelberg, 69120

  • Novartis Investigative Site

    Homburg, 66421

  • Novartis Investigative Site

    Kiel, 24105

  • Novartis Investigative Site

    Leipzig, Saxony, 04103

  • Novartis Investigative Site

    Mainz, 55131

  • Novartis Investigative Site

    Mannheim, Baden-Wurttemberg, 68305

  • Novartis Investigative Site

    Marburg, 35039

  • Novartis Investigative Site

    Minden, 32429

  • Novartis Investigative Site

    München, 81377

  • Novartis Investigative Site

    Münster, 48157

  • Novartis Investigative Site

    Regensburg, Bavaria, 93053

  • Novartis Investigative Site

    Stade, 21682

  • Novartis Investigative Site

    Tübingen, 72076

Other trials in Germany

Italy17 sites

  • Novartis Investigative Site

    Bari, BA, 70124

  • Novartis Investigative Site

    Bergamo, BG, 24127

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Brescia, BS, 25123

  • Novartis Investigative Site

    Candiolo, TO, 10060

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Meldola, FC, 47014

  • Novartis Investigative Site

    Milan, MI, 20133

  • Novartis Investigative Site

    Milan, MI, 20141

  • Novartis Investigative Site

    Modena, MO, 41124

  • Novartis Investigative Site

    Monza, MB, 20900

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Padova, PD, 35100

  • Novartis Investigative Site

    Roma, RM, 00167

  • Novartis Investigative Site

    Siena, SI, 53100

  • Novartis Investigative Site

    Torino, TO, 10126

  • Novartis Investigative Site

    Verona, VR, 37134

Other trials in Italy

Spain13 sites

  • Novartis Investigative Site

    A Coruña, Galicia, 15006

  • Novartis Investigative Site

    Badalona, Catalonia, 08916

  • Novartis Investigative Site

    Barcelona, Catalonia, 08036

  • Novartis Investigative Site

    Jerez de la Frontera, Cadiz, 11407

  • Novartis Investigative Site

    Las Palmas de Gran Canaria, 35016

  • Novartis Investigative Site

    Madrid, 28009

  • Novartis Investigative Site

    Madrid, 28034

  • Novartis Investigative Site

    Madrid, 28050

  • Novartis Investigative Site

    Madrid, 28222

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

  • Novartis Investigative Site

    Oviedo, Principality of Asturias, 33011

  • Novartis Investigative Site

    Seville, Andalusia, 41009

  • Novartis Investigative Site

    Valencia, Valencia, 46014

Other trials in Spain

United States12 sites

  • California Cancer Associates for Research and Excellence

    Encinitas, California, 92024

  • Univ of TX MD Anderson Cancer Cntr

    Houston, Texas, 77030

  • University of Tennessee Medical Ctr

    Knoxville, Tennessee, 37920

  • Johns Hopkins U

    Lutherville, Maryland, 21093

  • NYU Laura and Isaac Perlmutter Cancer Center

    New York, New York, 10016

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

  • UC Irvine Medical Center

    Orange, California, 92613-4091

  • University of Pittsburgh Med Center

    Pittsburgh, Pennsylvania, 15213

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • California Pacific Medical Center

    San Francisco, California, 94115

  • Stanford Cancer Center

    Stanford, California, 94305

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

United Kingdom9 sites

  • Novartis Investigative Site

    Guildford, Surrey, GU2 7XX

  • Novartis Investigative Site

    Leicester, LE1 5WW

  • Novartis Investigative Site

    London, NW3 2QG

  • Novartis Investigative Site

    Manchester, M20 2BX

  • Novartis Investigative Site

    Middlesbrough, TS4 3BW

  • Novartis Investigative Site

    Preston, PR2 9HT

  • Novartis Investigative Site

    Rickmansworth Road, WD187HT

  • Novartis Investigative Site

    Sutton, Surrey, SM2 5PT

  • Novartis Investigative Site

    Truro, Cornwall, TR1 3LJ

Other trials in United Kingdom

Russia8 sites

  • Novartis Investigative Site

    Chelyabinsk, 454048

  • Novartis Investigative Site

    Moscow, 115478

  • Novartis Investigative Site

    Moscow, 143423

  • Novartis Investigative Site

    Nizhny Novgorod, 603137

  • Novartis Investigative Site

    Omsk, 644013

  • Novartis Investigative Site

    Saint Petersburg, 197758

  • Novartis Investigative Site

    Saint Petersburg, 198255

  • Novartis Investigative Site

    Samara, 443011

Other trials in Russia

Czechia7 sites

  • Novartis Investigative Site

    Brno, Czech Republic, 656 53

  • Novartis Investigative Site

    Hradec Králové, CZE, 500 05

  • Novartis Investigative Site

    Olomouc, 779 00

  • Novartis Investigative Site

    Ostrava, Poruba, 708 52

  • Novartis Investigative Site

    Prague, 100 34

  • Novartis Investigative Site

    Prague, 12808

  • Novartis Investigative Site

    Zlín, Czech Republic, 762 75

Other trials in Czechia

Australia5 sites

  • Novartis Investigative Site

    Gateshead, New South Wales, 2290

  • Novartis Investigative Site

    Greenslopes, Queensland, 4120

  • Novartis Investigative Site

    Melbourne, Victoria, 3004

  • Novartis Investigative Site

    Nedlands, Western Australia, 6009

  • Novartis Investigative Site

    North Sydney, New South Wales, 2060

Other trials in Australia

Austria5 sites

  • Novartis Investigative Site

    Graz, 8036

  • Novartis Investigative Site

    Innsbruck, Tyrol, 6020

  • Novartis Investigative Site

    Linz, 4020

  • Novartis Investigative Site

    Salzburg, A-5020

  • Novartis Investigative Site

    Sankt Pölten, 3100

Other trials in Austria

Canada5 sites

  • Novartis Investigative Site

    Montreal, Quebec, H3T 1E2

  • Novartis Investigative Site

    Montreal, Quebec, H4A 3J1

  • Novartis Investigative Site

    Sherbrooke, Quebec, J1H 5N4

  • Novartis Investigative Site

    Toronto, Ontario, M4N 3M5

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Japan5 sites

  • Tokyo Metropolitan Komagome Hospital

    Bunkyo Ku, Tokyo, 113-8677

  • National Cancer Hospital

    Chuo Ku, Tokyo, 104 0045

  • Kyushu University Hospital

    Fukuoka, Fukuoka, 812-8582

  • Osaka International Cancer Institute

    Osaka, Osaka, 541-8567

  • Kyoto University Hospital

    Sakyo Ku, Kyoto, 606 8507

Other trials in Japan

Argentina4 sites

  • Novartis Investigative Site

    Caba, C1431FWO

  • Novartis Investigative Site

    CABA, Buenos Aires, C1125ABD

  • Novartis Investigative Site

    CABA, Buenos Aires, C1426ANZ

  • Novartis Investigative Site

    Rosario, Santa Fe Province, S2000KZE

Other trials in Argentina

Brazil4 sites

  • Novartis Investigative Site

    Curitiba, Paraná, 80530 010

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90035-003

  • Novartis Investigative Site

    Rio de Janeiro, 20560-120

  • Novartis Investigative Site

    São Paulo, São Paulo, 01246 000

Other trials in Brazil

Chile3 sites

  • Novartis Investigative Site

    Santiago, 7500921

  • Novartis Investigative Site

    Santiago, 8420383

  • Novartis Investigative Site

    Temuco, Araucania, 4810469

Other trials in Chile

Hungary3 sites

  • Novartis Investigative Site

    Budapest, H 1122

  • Novartis Investigative Site

    Debrecen, 4032

  • Novartis Investigative Site

    Szeged, H 6725

Other trials in Hungary

Israel3 sites

  • Novartis Investigative Site

    Haifa, 3109601

  • Novartis Investigative Site

    Jerusalem, 9112001

  • Novartis Investigative Site

    Ramat Gan, 5265601

Other trials in Israel

Mexico3 sites

  • Novartis Investigative Site

    Guadalajara, Jalisco, 44100

  • Novartis Investigative Site

    León, Guanajuato, 37178

  • Novartis Investigative Site

    Mexico City, Mexico City, 14080

Other trials in Mexico

Sweden3 sites

  • Novartis Investigative Site

    Gothenburg, SE-413 45

  • Novartis Investigative Site

    Lund, 221 85

  • Novartis Investigative Site

    Stockholm, SE 171 76

Other trials in Sweden

Belgium2 sites

  • Novartis Investigative Site

    Brussels, 1090

  • Novartis Investigative Site

    Brussels, 1200

Other trials in Belgium

Bulgaria2 sites

  • Novartis Investigative Site

    Plovdiv, 4004

  • Novartis Investigative Site

    Sofia, 1303

Other trials in Bulgaria

Greece2 sites

  • Novartis Investigative Site

    Athens, 115 27

  • Novartis Investigative Site

    Athens, 18547

Other trials in Greece

Netherlands2 sites

  • Novartis Investigative Site

    Amersfroort, 3818 ES

  • Novartis Investigative Site

    Leiden, South Holland, 2333

Other trials in Netherlands

Poland2 sites

  • Novartis Investigative Site

    Gdansk, 80 952

  • Novartis Investigative Site

    Warsaw, 02 781

Other trials in Poland

Portugal2 sites

  • Novartis Investigative Site

    Lisbon, 1099 023

  • Novartis Investigative Site

    Porto, 4200-072

Other trials in Portugal

Switzerland2 sites

  • Novartis Investigative Site

    Aarau, Canton of Aargau, 5001

  • Novartis Investigative Site

    Zurich, 8091

Other trials in Switzerland

Thailand2 sites

  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Songkhla, Hat Yai, 90110

Other trials in Thailand

Denmark1 site

  • Novartis Investigative Site

    Aarhus N, 8200

Other trials in Denmark

Norway1 site

  • Novartis Investigative Site

    Oslo, 0310

Other trials in Norway

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Phase III Study Comparing the Combination of PDR001, Dabrafenib and Trametinib Versus Placebo, Dabrafenib and Trametinib in Previously Untreated Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

The purpose of this study was to evaluate safety and efficacy of the combination of an anti-PD-1 antibody (PDR001), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in patients with BRAF V600 mutant, unresectable and metastatic melanoma.

Read the detailed description

This study was designed as a phase III, multi-center study consisting of 3 parts:

  • Part 1: Safety run-in part The safety run-in part aimed to determine the recommended regimen of PDR001 in combination with dabrafenib and trametinib for previously untreated patients with BRAF V600 mutant unresectable or metastatic melanoma (stage IIIC/IV). Spartalizumab was administered at a starting dose level (DL1) of 400 mg every 4 weeks (Q4W), along with fixed doses of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily). The RP3R for Part 3 was determined using the Bayesian Logistic Regression Model (BLRM) with escalation with overdose control (EWOC) criteria.
  • Part 2: Biomarker cohort Part 2 was run to explore changes in the immune microenvironment and biomarker modulations upon treatment with the combination of dabrafenib, trametinib and PDR001. Part 2 started when the fourth subject in dose level 1 (DL1) of Part 1 completed approximately 4 weeks of study treatment, and fewer than 3 dose-limiting toxicities (DLTs) were observed. Participants in Part 2 received PDR001 (spartalizumab) at a dosage of 400 mg Q4W, in combination with dabrafenib (150 mg BID) and trametinib (2 mg QD).
  • Part 3: Double-blind, randomized, placebo-controlled part Part 3 was comparing the efficacy and safety of spartalizumab in combination with dabrafenib and trametinib to placebo in combination with dabrafenib and trametinib. Part 3 was initiated after determining the RP3R for the combination of spartalizumab with dabrafenib and trametinib in Part 1. Subjects were randomized in a 1:1 ratio to receive either the RP3R dose of spartalizumab identified in Part 1 or placebo, along with dabrafenib (150 mg BID) and trametinib (2 mg QD).

For all parts of the study, the treatment continued until the subject experiences any of the following events: disease progression according to RECIST 1.1 as determined by the Investigator, unacceptable toxicity, initiation of a new anti-neoplastic therapy, pregnancy, withdrawal of consent, physician's decision, loss to follow-up, death, or termination of the study by the Sponsor. Safety evaluations are conducted for all subjects for up to 150 days after the last dose of spartalizumab/placebo (safety follow-up period).

Subjects who discontinued study treatment without disease progression as per RECIST 1.1 continued with tumor assessments according to the protocol until documented disease progression, withdrawal of consent, loss to follow-up, or death, regardless of the initiation of new anti-neoplastic therapy (efficacy follow-up period).

Subjects entered the survival follow-up period after completing the safety follow-up period or experiencing disease progression as per RECIST 1.1 or response criteria for immunotherapy, whichever period is longer (survival follow-up period).

Conditions
Melanoma
Being tested
Spartalizumab, Placebo, Dabrafenib, Trametinib
Keywords
Spartalizumab (PDR001), dabrafenib, trametinib, melanoma, immunotherapy, PD 1 inhibitor, anti PD1, PD-1, anti-PD-1, combination treatment, malignant skin cancer, skin cancer, BRAF V600, unresectable BRAF V600 mutated melanoma, metastatic BRAF V600 mutated melanoma
Medical subject headings
Melanoma, Skin Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SpartalizumabBiological

    Also called PDR001

    Spartalizumab powder for solution is used in Part 1 and Part 2, and as concentrate for solution for infusion for Part 3. Spartalizumab is administered via intravenous infusion over 30 minutes once every 4 weeks

  • PlaceboOther

    Placebo is administered via intravenous infusion over 30 minutes once every 4 weeks

  • DabrafenibDrug

    Dabrafenib 150 mg capsules BID is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions.

  • TrametinibDrug

    Trametinib 2 mg tablets QD is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions

Study groups in NCT02967692
Study groupRoleWhat they receive
Part 1: Safety run-in CohortExperimentalIn Part 1, participants are treated at different dose levels to determine the recommended Phase 3 regimen of spartalizumab in combination with dabrafenib and trametinib. The starting dose of spartalizumab is 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
Receives: Biological: Spartalizumab; Drug: Dabrafenib; Drug: Trametinib
Part 2: Biomarker cohortExperimentalIn Part 2, participants are treated with spartalizumab 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
Receives: Biological: Spartalizumab; Drug: Dabrafenib; Drug: Trametinib
Part 3- Arm 1: Spartalizumab in combination with dabrafenib and trametinibExperimentalIn Part 3, participants are randomized to receive spartalizumab at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)
Receives: Biological: Spartalizumab; Drug: Dabrafenib; Drug: Trametinib
Part 3- Arm 2: Placebo in combination with dabrafenib and trametinibPlacebo comparatorIn Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)
Receives: Other: Placebo; Drug: Dabrafenib; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)

    DLT was defined as an adverse event or abnormal laboratory value that was unrelated to disease, disease progression, inter-current illness, or concomitant medications and occured within 8 weeks of treatment with spartalizumab in combination with dabrafenib and trametinib. The DLT criteria included Grade 4 hematological adverse events, Grade 4 bilirubin elevation, specific gastrointestinal adverse events, symptomatic serum amylase or lipase elevation, Grade 3 or higher hypertension, Grade 3 or higher cardiac events, Grade 2 or higher pneumonitis, Grade 3 or higher immune-related toxicities, infusion-related reactions, other clinically significant adverse events, and toxicities leading to a dosing delay of over 12 weeks. NCI CTCAE v4.03 was used for grading DLTs

    Measured: Up to 8 weeks (Part 1)

  2. Biomarker Cohort (Part 2): Change From Baseline in Programmed Cell Death-ligand 1 (PD-L1) Expression Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib

    Change from baseline in PD-L1 expression (as determined by immunohistochemistry in tissue samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2

    Measured: Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days

  3. Biomarker Cohort (Part 2): Change From Baseline in CD8+ Cells Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib

    Change from baseline in CD8+ cells (as determined by flow cytometry in blood samples) upon treatment with spartalizumab in combination with dabrafenib and trametinib in participants from Part 2

    Measured: Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days

  4. Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1

    Progression-free survival was defined as the time from the date of first dose to the date of the first documented radiological progression per investigator's assessment according to RECIST 1.1 or death due to any cause. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment.

    Measured: Up to disease progression or death due to any cause, whichever occurs first, assessed up to 2.8 years (Part 3)

Secondary outcomes (20)

  1. Overall Survival (OS)

    Overall survival was defined as the time from date of randomization to date of death due to any cause

    Measured: Up to death due to any cause, assessed up to approximately 7 years

  2. Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1

    ORR was defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters

    Measured: Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 years

  3. Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1

    DOR was defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria. The distribution of DOR was estimated using the KM method. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters

    Measured: From first documented response to date of first documented progression or death, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3)

  4. Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1

    DCR was defined as the percentage of participants with CR or PR or subjects with stable disease (SD) lasting for a duration of at least 24 weeks as per local review according to RECIST 1.1 criteria. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.

    Measured: Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 year

  5. Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status Scores

    The EORTC QLQ-C30 was a 30-item questionnaire that patients complete, consisting of both multi-item scales and single-item measures. It included five functional scales, three symptom scales, six single items, and a Global Health Status/Quality of Life (GHS/QoL) scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The change from baseline in GHS/QoL scores was calculated. A positive change from baseline indicated improvement in the patient's quality of life.

    Measured: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)

  6. Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Physical Functioning Scale Scores

    The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 physical functioning scale measured a patient's ability to carry out daily activities and tasks requiring physical exertion. It consisted of five questions asking patients to rate their level of physical functioning, with response options ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating better physical functioning. The change from baseline in physical functioning scale scores was calculated. A positive change from baseline indicated improvement in physical functioning.

    Measured: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)

  7. Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Pain Symptom Scale Scores

    The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The EORTC QLQ-C30 pain symptom scale was one of the symptom scales in the questionnaire, which measured the severity of pain experienced by the patient. The pain symptom scale consisted of two items, one measuring the severity of pain and the other measuring the use of painkillers. The items were rated on a 4-point scale ranging from 1="not at all" to 4="very much". The scores for each item were summed and transformed to a 0 to 100 scale, with higher scores indicating more severe pain. The change from baseline in pain symptom scale scores was calculated. A negative change from baseline indicated improvement.

    Measured: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)

  8. Randomized (Part 3): Time to 10 Point Definitive Deterioration in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status

    The EORTC QLQ-C30 was a patient completed 30 item questionnaire that was composed of both multi-item scales and single-item measures. These included five functional scales, three symptom scales, six single items and a global health status/QoL scale. The GHS/QoL scale had seven possible response scores ranging from 1 (very poor) to 7 (excellent), which were averaged and transformed to a 0-100 scale. A higher score on this scale indicated a better quality of life. The time to definitive 10 point deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10 points relative to baseline worsening of the GHS/QoL score or death due to any cause. If a subject had not had an event, the time to deterioration was censored at the date of the last adequate assessment. The distribution was estimated using KM method.

    Measured: From baseline to date of at least 10 points relative to baseline worsening of the global health status score or death due to any cause, up to 2.8 years (Part 3)

  9. Randomized (Part 3): Change From Baseline in Function Assessment Cancer Therapy-melanoma (FACT-M) Melanoma Subscale Score

    The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) quality of life questionnaire was composed of the FACT-General (FACT-G) plus the Melanoma Subscale and the Melanoma Surgery Subscale, which complemented the general scale with items specific to quality of life (QoL) in melanoma. The Melanoma Subscale of FACT-M included 16 questions, with response options of 0= "Not at all", 1= "a little bit", 2= "somewhat", 3= "quite a bit" and 4= "very much". The FACT-M melanoma subscale score ranged from 0 to 64, with higher scores indicating a higher quality of life in relation to melanoma. The change from baseline in melanoma subscale scores was calculated. A positive change from baseline indicated improvement.

    Measured: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)

  10. Randomized (Part 3): Change From Baseline in EuroQoL 5-level Instrument (EQ-5D-5L)- Visual Analog Scale (VAS) Score

    The EQ-5D-5L is a standardized questionnaire used to assess health-related quality of life, and it includes a Visual Analog Scale (VAS). The VAS score is obtained by asking the individual to rate their current health status on a scale from 0 to 100, where 0 represents the worst possible health state and 100 represents the best possible health state. The change from baseline in EQ-5D-5L VAS score was calculated. A positive change from baseline indicates improvement in the health status.

    Measured: From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)

  11. Randomized (Part 3): PFS as Per Investigator's Assessment by RECIST 1.1 by PD-L1 Expression

    PFS was defined as the time from the date of first dose to the date of the first documented radiological progression as per investigator's assessment using RECIST 1.1 response criteria or death due to any cause. The distribution of PFS was estimated using the KM method. If a patient had not had an event at the time of data cut-off, progression-free survival was censored at the date of last adequate tumor assessment. PFS analysis was performed by PD-L1 status (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression.

    Measured: Up to disease progression or death due to any cause, up to 2.8 years (Part 3)

  12. Randomized (Part 3): OS by PD-L1 Expression

    Overall survival was defined as the time from date of randomization to date of death due to any cause. OS analysis was performed by PD-L1 subgroup (positive, negative) where a positive status was defined as having ≥ 1% expression and a negative status was defined as having < 1% expression.

    Measured: Up to death due to any cause, assessed up to approximately 7 years

  13. Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline

    Spartalizumab ADA prevalence at baseline was calculated as the percentage of participants who had an spartalizumab ADA positive result at baseline.

    Measured: Baseline

  14. Spartalizumab ADA Incidence

    Spartalizumab ADA incidence was calculated as the percentage of participants who were treatment-induced spartalizumab ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted spartalizumab ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

    Measured: Throughout study until 150 days after the last dose of spartalizumab, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3).

  15. Trough Concentration (Ctrough) for Spartalizumab

    Ctrough for spartalizumab refers to the serum concentration of spartalizumab immediately prior to the administration of a dose of spartalizumab on Day 1 of Cycle 2 and later cycles.

    Measured: Pre-infusion on Day 1 of each Cycle starting from Cycle 2, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days

  16. Pre-dose Plasma Concentration for Dabrafenib

    Plasma concentration of dabrafenib immediately prior to the administration of a dose of dabrafenib.

    Measured: Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days

  17. Pre-dose Plasma Concentration for Trametinib

    Plasma concentration of trametinib immediately prior to the administration of a dose of trametinib.

    Measured: Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days

  18. Number of Participants With Dose Interruptions

    Number of participants with dose interruptions for spartalizumab, dabrafenib and trametinib

    Measured: From baseline to end of treatment, assessed up to approximately 7 years

  19. Number of Participants With Dose Reductions

    Number of patients with dose reductions for spartalizumab, dabrafenib and trametinib

    Measured: From baseline to end of treatment, assessed up to approximately 7 years

  20. Relative Dose Intensity

    Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio (expressed as percentage) of dose intensity and planned dose intensity:

    • Spartalizumab (PDR001) = [Dose intensity (mg/4W) / planned dose intensity (mg/4W)]*100.
    • Trametinib and Dabrafenib = [Dose intensity (mg/day) / planned dose intensity (mg/day)]*100.

    Measured: From baseline to end of treatment, assessed up to approximately 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2016 (estimated)
  2. Study start17 Feb 2017
  3. Primary completion11 Aug 2020
  4. Study completion21 Aug 2024

Why it stopped: Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
568 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02967692
Sponsor's protocol ID
CPDR001F2301
Other IDs
2016-002794-35, 2016
Acronym
COMBI-i
Status last verified
Sep 2025
First submitted
16 Nov 2016
Last updated
18 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Ribas A, Robert C, Schadendorf D, Long GV, Tawbi H, Flaherty K, Ascierto PA, Nathan P, Rutkowski P, Leonov OV, Lorigan P, Prey S, Saponara M, Arance A, Gaudy-Marqueste C, Stroyakovskiy D, Lebbe C, Maio M, Del Vecchio M, Boghikian PS, Gutzmer R, Depenni R, Miskic M, Russo M, Dummer R. COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib in BRAF V600-Mutant Advanced Melanoma. J Clin Oncol. 2026 Aug 12:JCO2600528. doi: 10.1200/JCO-26-00528. Online ahead of print.

    PubMed 42585631

  • Tawbi HA, Robert C, Brase JC, Gusenleitner D, Gasal E, Garrett J, Savchenko A, Gorgun G, Flaherty KT, Ribas A, Dummer R, Schadendorf D, Long GV, Nathan PD, Ascierto PA. Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with BRAF V600-mutant melanoma: exploratory biomarker analyses from a randomized phase 3 trial (COMBI-i). J Immunother Cancer. 2022 Jun;10(6):e004226. doi: 10.1136/jitc-2021-004226.

    PubMed 35728875

  • Dummer R, Long GV, Robert C, Tawbi HA, Flaherty KT, Ascierto PA, Nathan PD, Rutkowski P, Leonov O, Dutriaux C, Mandala M, Lorigan P, Ferrucci PF, Grob JJ, Meyer N, Gogas H, Stroyakovskiy D, Arance A, Brase JC, Green S, Haas T, Masood A, Gasal E, Ribas A, Schadendorf D. Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma. J Clin Oncol. 2022 May 1;40(13):1428-1438. doi: 10.1200/JCO.21.01601. Epub 2022 Jan 14.

    PubMed 35030011

  • Dummer R, Lebbe C, Atkinson V, Mandala M, Nathan PD, Arance A, Richtig E, Yamazaki N, Robert C, Schadendorf D, Tawbi HA, Ascierto PA, Ribas A, Flaherty KT, Pakhle N, Campbell CD, Gusenleitner D, Masood A, Brase JC, Gasal E, Long GV. Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i. Nat Med. 2020 Oct;26(10):1557-1563. doi: 10.1038/s41591-020-1082-2. Epub 2020 Oct 5.

    PubMed 33020648

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Spartalizumab, Dabrafenib and Trametinib in people with Melanoma, run by Novartis Pharmaceuticals at 179 sites in 29 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 179 sites in France, Germany, Italy, Spain, United States and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Up to 8 weeks (Part 1)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02967692, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.

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