Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Trametinib

Dabrafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Single arm study with dabrafenib + trametinib combination therapy

Dabrafenib + Trametinib

Neyns Bart, MD, PhD

Patients with BRAF V600 mutant advanced melanoma benefit from treatment with a BRAF-inhibitor (e.g. dabrafenib, vemurafenib) and from combination of a BRAF- and MEK-inhibitor (e.g. dabrafenib and trametinib). Following initial tumor regression, progression is diagnosed in a majority of patients treated with BRAF-inhibitor mono-therapy within the first 12-months of therapy. Various molecular mechanisms that underlie the development of resistance to treatment with a BRAF-inhibitor have been reported. These mechanisms do not include secondary mutations in the BRAF-gene and therefore resistance to BRAF-inhibition could potentially be reversible when selective pressure by BRAF-inhibition is withheld for a sufficient period of time of melanoma progression. This clinical trial protocol addresses the potential renewed anti-tumor activity of combined BRAF- and MEK inhibition with the combination of dabrafenib and trametinib in patients with unresectable AJCC stage III or - IV BRAF V600 mutant melanoma who are documented with progression of disease at least 12 weeks following the last day of dosing of a BRAFinhibitor containing treatment regimen.

Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients

A Phase II Clinical Trial on the Combination of Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients With Advanced BRAF V600 Mutant Melanoma

To explore if tumor specific cfDNA levels can be used as a monitoring tool to detect early progression of disease

Universitair Ziekenhuis Brussel

Bart Neyns, MD PhD

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Lipid Regulating Agents

Bone Density Conservation Agents

Midazolam

Rosuvastatin Calcium

Calcium

Calcium, Dietary

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

On Day 1 subjects will simultaneously receive single dose of Rosuvastatin 10 mg tablet and Midazolam 3 mg syrup administered orally in the morning.

Commercially available Rosuvastatin 10 mg tablets will be supplied. Single oral dose of Rosuvastatin 10 mg will be administered on Day 1, 8 and 22

Rosuvastatin10 mg tablet

Commercially available Midazolam syrup will be supplied.Single oral dose of Midazolam 3 mg syrup will be administered on Days 1, 8 and 22

Midazolam 3 mg syrup

Dabrafenib 75mg will be supplied in the form of capsules. Oral dose Dabrafenib 150 mg (2 x 75 mg) BID will be administered at 12 h apart on Days 8 through 22 and 150 mg (2 x 75 mg) OD on Day 23.

Dabrafenib 75 mg capsule

GSK Clinical Trials

This is an open-label, multi-center, fixed sequence study in subjects with BRAF V600 mutation positive tumors. Subjects will receive single oral doses of 10 milligram (mg) of rosuvastatin and 3 mg of midazolam in the morning of Day 1 (alone), Day 8 (with first dose of dabrafenib 150 mg), and Day 22 (during repeat dose dabrafenib 150 mg twice daily \[BID\]). Dabrafenib 150 mg BID will be administered from Day 8 to Day 23. Blood samples for PK analysis will be obtained over 32 hours post-dose on Day 1, Day 8, and Day 22. The last dose of dabrafenib will be taken in the morning of Day 23 and the last blood sample in the evening of Day 23. Subjects will be considered to have completed the study once the 32 hour PK sample has been collected on Day 23. Once they have completed the study, eligible subjects may have the option to enter study BRF114144, an open-label roll-over study of dabrafenib (no follow-up visit required) and continue receiving dabrafenib.

Effects of Dabrafenib on the Single Dose Pharmacokinetics (PK) of Rosuvastatin and Midazolam

An Open-label Phase 1 Study to Evaluate the Effects of Dabrafenib (GSK2118436) on the Single Dose Pharmacokinetics of an OATP1B1/1B3 Substrate and of a CYP3A4 Substrate in Subjects With BRAF V600 Mutation Positive Tumors

Blood samples will be collected for assessment of PK parameters including maximum observed concentration (Cmax), time to Cmax (tmax), and area under the concentration-time curve from pre-dose extrapolated to infinite time (AUC\[0-infinity\])

Blood samples will be collected for assessment of PK parameters including area under the concentration-time curve to time of last measurable concentration (AUC\[0-t\]), area under the concentration-time curve from time zero to a time point determined from the data (AUC (partial), terminal phase half-life (t1/2)

Blood samples will be collected for assessment of concentration of dabrafenib and its metabolites

AE is defined as Any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)

Vital sign measurements will include systolic and diastolic blood pressure, respiratory rate, pulse rate and pulse oximetry Vital signs should be measured after sitting in a semi-supine position for at least 5 min.

Cardiac assessments include 12-lead Electrocardiogram (ECG)

GlaxoSmithKline

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Genomic Instability

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Myotonic Dystrophy Type 1

Pharmaceutical Solutions

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Trastuzumab

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Immunomodulating Agents

Atezolizumab

Alectinib

Ado-Trastuzumab Emtansine

Vemurafenib

Adenosine

Maytansine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Tyrosine Kinase Inhibitors

Tyrosine

MPDL3280A 1200mg IV infusion - 3 weekly until progression or unacceptable toxicity.

Or in combination with chemotherapy:

* For non-squamous: Cisplatin or Carboplatin plus pemetrexed \& MPDL3280A - 3 weekly for 4 cycles followed by MPDL3280A and pemetrexed 3 weekly until progression or unacceptable toxicity or completion of a total of 35 cycles. MPDL3280A will then continue 3 weekly until progression or unacceptable toxicity.
* For squamous: Carboplatin plus paclitaxel \& MPDL3280A - 3 weekly for 4 cycles followed by MPDL3280A 3 weekly until progression or unacceptable toxicity.

Trastuzumab emtansine (T-DM1) 3.6mg/kg - 3 weekly until PD IV infusion

Intravenous (IV) infusion, as monotherapy of in combination with chemotherapy

MPDL3280A

Powder for concentrate for solution for infusion

Trastuzumab emtansine

Charles Swanton

DARWIN II is a multi-arm non-randomised phase II trial, Eligible patient will be those who relapse with NSCLC (clinical trials.gov ref. NCT02183883). .

The trial will investigate assess if intra-tumour heterogeneity (clonal vs subclonal actionable mutation) is associated with PFS.

Patients without an actionable mutation will receive MPDL3280A (atezolizumab), a monoclonal antibody targeting anti-PDL1, as monotherapy or in combination with chemotherapy, The options for combination therapy will vary depending on the histology of the NSCLC (i.e. non-squamous or squamous).

Patients with BRAFV600 mutations, HER2 Amplification, ALK/RET gene rearrangements will be enrolled into arms treating with vemurafenib, trastuzumab emtansine and alectinib respectively.

DARWIN II will include extensive exploratory biomarker analysis to investigate a number of genomic and immune markers that may predict response to MPDL3280A (atezolizumab) and help guide future clinical trial design.

DARWIN II is an exploratory phase II study examining the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy.

It will examine how clonal dominance and intratumour heterogeneity influence outcomes after treatment, offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1. These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC. The relationship between intratumour heterogeneity and cfDNA/CTCs will also be explored in DARWIN II, which may develop tools for patient selection and monitoring to be examined further in future studies. Results from DARWIN II will help to identify a biomarker for anti-PD-L1 therapy which could be used for patient stratification in future phase III trials of molecules targeting this T-cell inhibitory checkpoint. DARWIN II will also provide preliminary data on efficacy of MPDL3280A, which could be used to design randomised studies.

This is a multicentre non-randomised phase II study based on patients with relapsed NSCLC, who have provided a biopsy sample at the time of relapse.

The study arms:

* Arm 1: Patients without an actionable mutation - MPDL3280A (atezolizumab) monotherapy or in combination with chemptherapy
* Arm 2: BRAFV600 - vemurafenib
* Arm 3: ALK/RET gene rearrangement - alectinib
* Arm 4: HER2 Amplification - trastuzumab emtansine

Arms 2-4 are closed to further recruitment as of 25th May 2021.

Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity

Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity - DARWINII

Defined as the period between the date of registration to the date of subsequent progression or death (whichever occurs first)

Investigator-assessed according to RECISTv1.1 and irRC (Arm 1 only)

Period between first complete response or partial response until the first date recurrence or progressive disease, assessed up to 84 months

Dose reductions, interruptions, modifications and exposure

Interrogation of recurrence and progression biopsies to decipher the molecular basis for resistance in combination with analyses of CTCs/cfDNA as well as CT imaging heterogeneity analyses

Hoffmann-La Roche

University College, London

Antibodies

Immunoglobulins

Spartalizumab

In 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).

In 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).

In 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)

In 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)

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

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

Placebo

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

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

Novartis Pharmaceuticals

To evaluate the safety and efficacy of the combination of an anti-PD-1 antibody (Spartalizumab (PDR001)), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in unresectable or metastatic BRAF V600 mutant melanoma

This study is designed as a Phase III, multi-center study consisting of three parts:

* Part 1, known as the Safety Run-in, is an open-label part aimed at determining the recommended Phase III regimen (RP3R) of spartalizumab in combination with dabrafenib and trametinib for previously untreated subjects with BRAF V600 mutant unresectable or metastatic melanoma (Stage IIIC/IV per AJCC edition 7). In Part 1, 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, referred to as the Biomarker Cohort, is an open-label section focused on characterizing the kinetics of immune biomarkers and potential immune resistance mechanisms. 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 receive PDR001 (spartalizumab) at a dosage of 400 mg Q4W, in combination with dabrafenib (150 mg BID) and trametinib (2 mg QD).
* Part 3 is a double-blind, randomized, placebo-controlled phase that compares 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 is 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 discontinue study treatment without disease progression as per RECIST 1.1 continue 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 enter 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).

Part 1 and Part 2 are open- label. Part 3 is double-blind and randomized.

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

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

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

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

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

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

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.

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

OS is defined as the time from date of randomization to date of death due to any cause.

OS analysis will be performed by PD-L1 subgroup (positive, negative) where a positive status is defined as having ≥ 1% expression and a negative status is defined as having \< 1% expression.

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

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)

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.

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

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

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

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

Relative dose intensity for spartalizumab, dabrafenib and trametinib computed as the ratio of dose intensity and planned dose intensity

Treatment-emergent Adverse Events: Any sign or symptom that occured during the study treatment plus 30 days post treatment in the Safety Set (treated patients only). All-Cause Mortality is using the Full Analysis Set, including all participants to whom study treatment was assigned by randomization (Part 3) and all participants to whom study treatment was assigned and who received at least one one of any study treatment (Part 1 and 2)

Deaths were collected in the pre-treatment period (from day of patient's informed consent to the day before first administration of study treatment )

All Participants (Pre-treatment)

AEs during on-treatment period and post-treatment safety follow-up (up to 150 days post-treatment)

Part 1: Safety run-in Cohort (On-treatment and Post-treatment Safety FU)

Deaths collected in the post-treatment survival follow-up period (starting from day 151 post- treatment). No AEs were collected during this period

Part 1: Safety run-in Cohort (Post-treatment Survival FU)

Part 2: Biomarker Cohort (On-treatment and Post-treatment Safety FU)

Part 2: Biomarker Cohort (Post-treatment Survival FU)

Part 3- Arm 1: Spartalizumab + Dabrafenib + Trametinib (On-treatment and Post-treatment Safety FU)

Part 3- Arm 1: Spartalizumab + Dabrafenib +Trametinib (Post-treatment Survival FU)

Part 3- Arm 2: Placebo + Dabrafenib + Trametinib (On-treatment and Post-treatment Safety FU)

Part 3- Arm 2: Placebo + Dabrafenib + Trametinib (Post-treatment Survival FU)

In Part 1, participants are treated with spartalizumab 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).

Part 1- Safety run-in: Spartalizumab 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD

Part 2- Biomarker Cohort: Spartalizumab 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD

Part 3- Arm 1: Spartalizumab 400 mg Q4W + Dabrafenib 150 mg BID + Trametinib 2 mg QD

Part 3- Arm 2: Placebo + Dabrafenib 150 mg BID + Trametinib 2 mg QD

Total

Age, Categorical

Sex: Female, Male

Race/Ethnicity, Customized

Study Director

Dose-Determining Set (DDS) including all subjects in Part 1 who received at least one dose of study treatment who either 1) met the minimum exposure criterion and had sufficient safety evaluations, or 2) experienced a DLT during the first 8 weeks (56 days) of spartalizumab in combination with dabrafenib and trametinib dosing.

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

Cycle 1 Day 15

Cycle 3 Day 1

Participants in Part 2 who received at least one dose of study treatment and with evaluable data at the pre-specified time points

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients	NCT02296996	Malignant Melan...	Dabrafenib + Tr...	18 Years -	Universitair Ziekenhuis Brussel
Effects of Dabrafenib on the Single Dose Pharmacokinetics (PK) of Rosuvastatin and Midazolam	NCT02082665	Cancer	Rosuvastatin10 ... Midazolam 3 mg ... Dabrafenib 75 m...	18 Years - 65 Years	GlaxoSmithKline
Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity	NCT02314481	Non-small Cell ...	MPDL3280A Vemurafenib Alectinib Trastuzumab emt...	18 Years -	University College, London
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma	NCT02967692	Melanoma	Spartalizumab Placebo Dabrafenib Trametinib	18 Years -	Novartis
Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer	NCT04061980	BRAF NP_004324.... BRAF V600E Muta... Metastatic Thyr... Refractory Thyr... Stage IV Differ... Stage IVA Diffe... Stage IVB Diffe...	Binimetinib Encorafenib Nivolumab	18 Years -	Providence Health & Services
A Pharmacokinetics (PK) Study of the Effects Rabeprazole and Rifampin on Dabrafenib in Subjects With BRAF V600 Mutation Positive Tumors	NCT01954043	Cancer	Dabrafenib 150 ... Rabeprazole 40 ... Rifampin 600 mg...	18 Years -	GlaxoSmithKline
Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer	NCT04061980	BRAF NP_004324.... BRAF V600E Muta... Metastatic Thyr... Refractory Thyr... Stage IV Differ... Stage IVA Diffe... Stage IVB Diffe...	Binimetinib Encorafenib Nivolumab	18 Years -	Providence Health & Services
A Pharmacokinetics (PK) Study of the Effects Rabeprazole and Rifampin on Dabrafenib in Subjects With BRAF V600 Mutation Positive Tumors	NCT01954043	Cancer	Dabrafenib 150 ... Rabeprazole 40 ... Rifampin 600 mg...	18 Years -	GlaxoSmithKline
Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients	NCT02296996	Malignant Melan...	Dabrafenib + Tr...	18 Years -	Universitair Ziekenhuis Brussel
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma	NCT02967692	Melanoma	Spartalizumab Placebo Dabrafenib Trametinib	18 Years -	Novartis

Spots Global Cancer Trial Database for braf v600

Every month we try and update this database with for braf v600 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for braf v600

Every month we try and update this database with for braf v600 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for braf v600 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.