Cancer
Conditions
Keywords
solid tumors, anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2) glioma (LGG), high grade (WHO G3/G4) glioma (HGG), non-seminomatous germ cell tumors (NSGCT)/non-germinomatous germ cell tumors (NGGCT), adenocarcinoma of the small intestine (ASI), hairy cell leukemia (HCL), multiple myeloma (MM), efficacy, safety, BRAF V600E mutation, Trametinib, Dabrafenib
Brief summary
This was a Phase II, open-label, non-randomized, multi-center study of oral dabrafenib in combination with oral trametinib in subjects with rare cancers harboring the BRAF V600E mutation including anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2) glioma (LGG), high grade (WHO G3/G4) glioma (HGG), non-seminomatous germ cell tumors (NSGCT) / non-germinomatous germ cell tumors (NGGCT), adenocarcinoma of the small intestine (ASI), hairy cell leukemia (HCL) and multiple myeloma (MM).
Detailed description
This study was designed to determine the overall response rate (ORR) of oral Dabrafenib in combination with oral Trametinib in subjects with rare BRAF V600E mutated cancers. Subjects needed to have a fresh or frozen tumor tissue sample provided to confirm the BRAF V600E mutation status. Only subjects with histologically confirmed advanced disease and no available standard treatment options were eligible for enrollment. Subjects underwent screening assessments within 14 days (up to 35 days for ophthalmology exam, echocardiogram or disease assessments) prior to the start of treatment to determine their eligibility for enrollment in the study. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, withdrawal of consent or death. Once a subject discontinued treatment, a post-treatment follow-up visit was conducted within 28 days (+ 7 days) after the last dose of study treatment(s). Extended follow-up visits were conducted every 4 weeks (+/- 7 days) for the first 6 months and then every 3 months (+/- 14 days) thereafter. A subject was considered to have discontinued the study if the subject was lost to follow-up or withdrew consent or another reason existed that prevented additional data from being collected on the subject. A subject was considered to have completed the study at the time of death. For each histology, up to 25 patients were planned to be enrolled in each of the 9 primary analysis cohorts. A cohort could be closed or stopped early (prior to capping at 25 patients) for futility or efficacy. An uncapped expansion cohort was planned when a particular cohort was stopped early for efficacy. All planned histology cohorts enrolled at least one subject, with the exception of the germ cell tumor cohort. Enrolment in the study was closed in July 2018.
Interventions
DRUGDabrafenib
A 150 mg twice daily capsule administered orally on a continuous basis.
DRUGTrametinib
A 2 mg once daily tablet administered orally on a continuous basis.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
9 indications: anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2) glioma (LGG), high grade (WHO G3/G4) glioma (HGG), non-seminomatous germ cell tumors (NSGCT)/non-germinomatous germ cell tumors (NGGCT), adenocarcinoma of the small intestine (ASI), hairy cell leukemia (HCL) and multiple myeloma (MM).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed, written informed consent. * Sex: male or female. * Age: \>=18 years of age at the time of providing informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status: 0, 1 or 2. * Must have advanced disease and no standard treatment options as determined by locally/regionally available standards of care and treating physician's discretion * Must have a a BRAF V600E mutation-positive tumor as confirmed by an approved local laboratory or a sponsor designated central reference laboratory. All subjects must provide an archived or fresh tumor sample (for solid tumors) or a fresh BM aspirate and peripheral blood sample (for HCL and MM) for confirmation testing of the BRAF V600E mutation by a sponsor designated central reference laboratory using a sponsor designated assay * Able to swallow and retain orally administered medication. NOTE: Subject should not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. For example, subjects should have no more than 50% of the large intestine removed and no sign of malabsorption (i.e., diarrhea).NOTE: If clarification is needed as to whether a condition will significantly affect the absorption of study treatments, contact the GSK Medical Monitor. * Female Subjects of Childbearing Potential: Subjects must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment and agrees to use effective contraception, throughout the treatment period and for 4 months after the last dose of study treatment. * French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Exclusion criteria
* Prior treatment with: BRAF and/or MEK inhibitor(s); anti-cancer therapy (e.g., chemotherapy with delayed toxicity, immunotherapy, biologic therapy or chemoradiation) within 21 days or prior nitrosourea or mitomycin C containing therapy within 42 days prior to enrollment and/or prior daily or weekly chemotherapy or biologic therapy without the potential for delayed toxicity within 14 days prior to enrolment or prior nvestigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to enrollment * History of malignancy with confirmed activating RAS mutation at any time. Prospective RAS testing is not required. However, if the results of previous RAS testing are known, then those results must be used in assessing eligibility. * Prior radiotherapy less than 14 days prior to enrollment, except for WHO Grade 1 4 glioma (radiotherapy is not permitted within 3 months prior to enrollment) and ATC (radiotherapy is not permitted within 7 days prior to enrollment). Treatment-related AEs must have resolved prior to enrollment. * Prior major surgery less than 14 days prior to enrollment. Any surgery-related AE(s) must have resolved prior to enrollment * Prior solid organ transplantation or allogenic stem cell transplantation (ASCT). However, previous autologous BM transplant (ABMT) or autologous peripheral blood stem cell transplant (PBSCT) is permitted. * History of another malignancy. Subjects with another malignancy are eligible if: (a) disease-free for 3 years, or (b) have a history of completely resected non-melanoma skin cancer, and/or (c) have an indolent second malignancy(ies). * Presence of brain metastases (except for subjects in the WHO Grade 1 or 2 or 3 or 4 glioma histology cohorts) that are symptomatic or untreated or not stable for \>=3 months (must be documented by imaging) or requiring corticosteroids. Subjects on a stable dose of corticosteroids \>14 days and have not required treatment with enzyme-inducing anticonvulsants for \>30 days prior to enrollment can be enrolled with approval of the Medical Monitor * Presence of symptomatic or untreated leptomeningeal or spinal cord compression. Subjects who have been previously treated for these conditions and have stable CNS disease (documented by consecutive imaging studies) for \>60 days, are asymptomatic and currently not taking corticosteroids, or have been on a stable dose of corticosteroids for at least 30 days prior to enrollment, are permitted * Presence of interstitial lung disease or pneumonitis * Presence of any unresolved \>=Grade 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version 4.0) toxicity from previous anti-cancer therapy at the time of enrollment, except alopecia or Grade 2 anemia. Subjects with MM who have ≤Grade 2 peripheral neuropathy (per CTCAE v4.0) are permitted. * Presence of any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures * History of retinal vein occlusion * Clinically significant GI abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. For example, subjects should have no more than 50% of the large intestine removed and no sign of malabsorption (i.e., diarrhea) * History or evidence of cardiovascular risk including any of the following: Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrolment; clinically significant uncontrolled arrhythmias; however, subjects with controlled atrial fibrillation for \>30 days prior to enrollment are eligible; class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) criteria; left ventricular ejection fraction (LVEF) below the institutional LLN. If a LLN does not exist at an institution, then use LVEF \<50%; abnormal cardiac valve morphology (≥Grade 2) documented by ECHO; however, subjects with Grade 1 abnormalities (i.e., mild regurgitation/stenosis) may be entered on study but subjects with moderate valvular thickening should NOT be enrolled; corrected QT (QTc) interval for heart rate using Bazett-corrected QT interval (QTcB) \>=480 msec; intracardiac defibrillator; treatment-refractory hypertension defined as a blood pressure (BP) \>140/90 mmHg which may not be controlled by anti-hypertensive medication(s) and/or lifestyle modifications * Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior exposure can be enrolled, only if a confirmatory negative Hepatitis C RNA polymerase chain reaction (PCR) test is obtained. * Current use of prohibited medication(s) or requirement for prohibited medications during study as per the study protocol. Use of anticoagulants such as warfarin is permitted; however, international normalization ratio (INR) must be monitored according to local institutional practice. * Clinically significant known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study treatment, or excipients, or to dimethyl sulfoxide (structural component of dabrafenib). * Pregnant, lactating or actively breastfeeding female subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Overall Response Rate (ORR) in the Gastrointestinal Stromal Tumor (GIST) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Overall Response Rate (ORR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (response assessment criteria (CR, PR, and minor response \[MR\]) WHO Grade 1 and 2 Glioma) by investigator assessment as defined by response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population. |
| Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (updated response assessment criteria (CR, PR) WHO Grade 3 and 4 Glioma) by investigator assessment as defined by modified response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population. |
| Overall Response Rate (ORR) in the Hairy Cell Leukemia (HCL) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with CR +/- minimal residual disease \[MRD\], PR by investigator assessment as defined by the Consensus Resolution Criteria adapted from the National Comprehensive Cancer Network (NCCN) guidelines. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population. |
| Overall Response Rate (ORR) in the Multiple Myeloma (MM) Cohort | From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Response Rate (ORR) was defined as the percentage of participants with stringent complete response (sCR), CR, PR, very good partial response (VGPR) by investigator assessment as defined by the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) in the Biliary Tract Cancer (BTC) Cohort | From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. |
| Progression Free Survival (PFS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. |
| Progression Free Survival (PFS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. |
| Progression Free Survival (PFS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. |
| Progression Free Survival (PFS) in the Hairy Cell Leukemia (HCL) Cohort | From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. |
| Progression Free Survival (PFS) in the Multiple Myeloma (MM) Cohort | From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. |
| Overall Survival (OS) in the Anaplastic Thyroid Cancer (ATC) Cohort | From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis. |
| Duration of Response (DoR) in the Anaplastic Thyroid Cancer (ATC) Cohort | From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment. |
| Overall Survival (OS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis. |
| Overall Survival (OS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis. |
| Overall Survival (OS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis. |
| Overall Survival (OS) in the Hairy Cell Leukemia (HCL) Cohort | From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis. |
| Overall Survival (OS) in the Multiple Myeloma (MM) Cohort | From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis. |
| Number of Participants With Adverse Events (AEs) | From study treatment start date till 30 days safety follow-up, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | The distribution of adverse events (AE) was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) through the monitoring of relevant clinical and laboratory safety parameters. |
| Overall Survival (OS) in the Biliary Tract Cancer (BTC) Cohort | From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis. |
| Duration of Response (DoR) in the Biliary Tract Cancer (BTC) Cohort | From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment. |
| Duration of Response (DoR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment. |
| Duration of Response (DoR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment. |
| Duration of Response (DoR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment. |
| Duration of Response (DoR) in the Hairy Cell Leukemia (HCL) Cohort | From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment. |
| Duration of Response (DoR) in the Multiple Myeloma (MM) Cohort | From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment. |
| Progression Free Survival (PFS) in the Anaplastic Thyroid Cancer (ATC) Cohort | From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21) | Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. |
Countries
Austria, Belgium, Canada, Denmark, France, Germany, Italy, Japan, Netherlands, Norway, South Korea, Spain, Sweden, United States
Participant flow
Recruitment details
The study was conducted in 41 centers in 14 countries worldwide.
Pre-assignment details
Subjects were enrolled into cohorts based on the type of histology. For each histology, up to 25 patients were planned to be enrolled. A cohort could be closed or stopped early (prior to capping at 25 patients) for futility or efficacy. An uncapped expansion cohort was planned when a particular cohort was stopped early for efficacy.
Participants by arm
| Arm | Count |
|---|---|
| Anaplastic Thyroid Cancer (ATC) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 36 |
| Biliary Tract Cancer (BTC) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 43 |
| Gastrointestinal Stromal Tumor (GIST) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 1 |
| Low Grade (WHO G1/G2) Glioma (LGG) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 13 |
| High Grade (WHO G3/G4) Glioma (HGG) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 45 |
| Adenocarcinoma of the Small Intestine (ASI) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 3 |
| Hairy Cell Leukemia (HCL) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 55 |
| Multiple Myeloma (MM) All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, or death. | 10 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 |
| Overall Study | Study closed by sponsor | 6 | 2 | 0 | 6 | 7 | 0 | 42 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 7 | 0 | 3 | 7 | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Multiple Myeloma (MM) | Hairy Cell Leukemia (HCL) | Anaplastic Thyroid Cancer (ATC) | Adenocarcinoma of the Small Intestine (ASI) | High Grade (WHO G3/G4) Glioma (HGG) | Low Grade (WHO G1/G2) Glioma (LGG) | Gastrointestinal Stromal Tumor (GIST) | Biliary Tract Cancer (BTC) |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.1 Years STANDARD_DEVIATION 16.4 | 66.9 Years STANDARD_DEVIATION 6.89 | 64.8 Years STANDARD_DEVIATION 10.77 | 69.6 Years STANDARD_DEVIATION 9.53 | 58.3 Years STANDARD_DEVIATION 3.21 | 41.9 Years STANDARD_DEVIATION 14.7 | 33.1 Years STANDARD_DEVIATION 11.51 | 77.0 Years | 57.0 Years STANDARD_DEVIATION 11.88 |
| ECOG Performance Status Grade 0 | 72 Participants | 3 Participants | 25 Participants | 4 Participants | 3 Participants | 14 Participants | 5 Participants | 1 Participants | 17 Participants |
| ECOG Performance Status Grade 1 | 118 Participants | 6 Participants | 27 Participants | 30 Participants | 0 Participants | 24 Participants | 7 Participants | 0 Participants | 24 Participants |
| ECOG Performance Status Grade 2 | 16 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 7 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 17 Participants | 1 Participants | 0 Participants | 11 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 7 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 10 Participants | 0 Participants | 6 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 5 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European heritage | 157 Participants | 8 Participants | 48 Participants | 17 Participants | 2 Participants | 32 Participants | 10 Participants | 1 Participants | 39 Participants |
| Sex: Female, Male Female | 90 Participants | 5 Participants | 8 Participants | 20 Participants | 1 Participants | 22 Participants | 9 Participants | 1 Participants | 24 Participants |
| Sex: Female, Male Male | 116 Participants | 5 Participants | 47 Participants | 16 Participants | 2 Participants | 23 Participants | 4 Participants | 0 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 36 | 6 / 43 | 0 / 1 | 1 / 13 | 2 / 45 | 0 / 3 | 4 / 55 | 1 / 10 | 18 / 30 | 28 / 37 | 1 / 1 | 3 / 12 | 26 / 43 | 3 / 3 | 4 / 51 | 8 / 9 |
| other Total, other adverse events | 36 / 36 | 43 / 43 | 1 / 1 | 12 / 13 | 42 / 45 | 3 / 3 | 55 / 55 | 9 / 10 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 20 / 36 | 17 / 43 | 1 / 1 | 3 / 13 | 16 / 45 | 0 / 3 | 32 / 55 | 4 / 10 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Response Rate (ORR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | Investigator assessment @ up to 78 months | 67 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | Investigator assessment @ up to 92 months | 67 Percentage of Participants |
Primary
Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort | Investigator assessment @ up to 78 months | 56 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort | Investigator assessment @ up to 92 months | 56 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort | Independent radiology review @ up to 78 months | 53 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort | Independent radiology review @ up to 92 months | 53 Percentage of Participants |
Primary
Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort | Investigator assessment @ up to 78 months | 53 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort | Investigator assessment @ up to 92 months | 53 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort | Independent radiology review @ up to 78 months | 47 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort | Independent radiology review @ up to 92 months | 47 Percentage of Participants |
Primary
Overall Response Rate (ORR) in the Gastrointestinal Stromal Tumor (GIST) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response \[CR\], partial response \[PR\]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Gastrointestinal Stromal Tumor (GIST) Cohort | Investigator assessment @ 78 months | 0 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Gastrointestinal Stromal Tumor (GIST) Cohort | Investigator assessment @ 92 months | 0 Percentage of Participants |
Primary
Overall Response Rate (ORR) in the Hairy Cell Leukemia (HCL) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with CR +/- minimal residual disease \[MRD\], PR by investigator assessment as defined by the Consensus Resolution Criteria adapted from the National Comprehensive Cancer Network (NCCN) guidelines. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Hairy Cell Leukemia (HCL) Cohort | Investigator assessment @ up to 78 months | 89 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Hairy Cell Leukemia (HCL) Cohort | Investigator assessment @ up to 92 months | 89 Percentage of Participants |
Primary
Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (updated response assessment criteria (CR, PR) WHO Grade 3 and 4 Glioma) by investigator assessment as defined by modified response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Investigator assessment @ up to 78 months | 33 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Investigator assessment @ up to 92 months | 33 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Independent radiology review @ up to 78 months | 31 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Independent radiology review @ up to 92 months | 31 Percentage of Participants |
Primary
Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (response assessment criteria (CR, PR, and minor response \[MR\]) WHO Grade 1 and 2 Glioma) by investigator assessment as defined by response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Investigator assessment/Response rate @ up to 78 months | 69 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Investigator assessment/Response rate @ up to 92 months | 69 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Independent radiology review/Response rate @ up to 78 months | 69 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Independent radiology review/Response rate @ up to 92 months | 62 Percentage of Participants |
Primary
Overall Response Rate (ORR) in the Multiple Myeloma (MM) Cohort
Overall Response Rate (ORR) was defined as the percentage of participants with stringent complete response (sCR), CR, PR, very good partial response (VGPR) by investigator assessment as defined by the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.
Time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Multiple Myeloma (MM) Cohort | Investigator assessment @ up to 78 months | 50 Percentage of Participants |
| Anaplastic Thyroid Cancer (ATC) | Overall Response Rate (ORR) in the Multiple Myeloma (MM) Cohort | Investigator assessment @ up to 92 months | 50 Percentage of Participants |
Secondary
Duration of Response (DoR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time frame: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort. Only responders were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | Investigator assessment | 33.4 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | Independent radiology review | 32.8 Weeks |
Secondary
Duration of Response (DoR) in the Anaplastic Thyroid Cancer (ATC) Cohort
For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time frame: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Anaplastic Thyroid Cancer (ATC) Cohort | Investigator assessment | 62.4 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Anaplastic Thyroid Cancer (ATC) Cohort | Independent radiology review | 59.1 Weeks |
Secondary
Duration of Response (DoR) in the Biliary Tract Cancer (BTC) Cohort
For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time frame: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Biliary Tract Cancer (BTC) Cohort | Investigator assessment | 38.9 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Biliary Tract Cancer (BTC) Cohort | Independent radiology review | 45.4 Weeks |
Secondary
Duration of Response (DoR) in the Hairy Cell Leukemia (HCL) Cohort
For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time frame: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Hairy Cell Leukemia (HCL) Cohort | NA Weeks |
Secondary
Duration of Response (DoR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time frame: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohorts combined. Only responders were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Investigator assessment | 135.7 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Independent radiology review | 59.3 Weeks |
Secondary
Duration of Response (DoR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time frame: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort. Only responders were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Investigator assessment | NA Weeks |
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Independent radiology review | 84.3 Weeks |
Secondary
Duration of Response (DoR) in the Multiple Myeloma (MM) Cohort
For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.
Time frame: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort. Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Duration of Response (DoR) in the Multiple Myeloma (MM) Cohort | 48.1 Weeks |
Secondary
Number of Participants With Adverse Events (AEs)
The distribution of adverse events (AE) was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: From study treatment start date till 30 days safety follow-up, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: All-treated Subjects (ATS) population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 6 Participants |
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | Any AE | 36 Participants |
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 27 Participants |
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 17 Participants |
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 19 Participants |
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | Any SAE | 20 Participants |
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 7 Participants |
| Anaplastic Thyroid Cancer (ATC) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 3 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 42 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 9 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 2 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 1 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 15 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 24 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | Any SAE | 17 Participants |
| Biliary Tract Cancer (BTC) | Number of Participants With Adverse Events (AEs) | Any AE | 43 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 1 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 0 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 0 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 1 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 1 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | Any AE | 1 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 0 Participants |
| Gastrointestinal Stromal Tumor (GIST) | Number of Participants With Adverse Events (AEs) | Any SAE | 1 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 4 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 2 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 1 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 6 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 0 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | Any SAE | 3 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 12 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | Number of Participants With Adverse Events (AEs) | Any AE | 12 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | Any AE | 42 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | Any SAE | 16 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 18 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 1 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 7 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 18 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 37 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 4 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 0 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 2 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 3 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 2 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 1 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | Any AE | 3 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 0 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 13 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 52 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | Any AE | 55 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 29 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 40 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | Any SAE | 32 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 3 Participants |
| Hairy Cell Leukemia (HCL) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 19 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | Fatal SAEs | 0 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | SAEs related to study treatment | 3 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | Any SAE | 4 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | AEs leading to dose interruption/delay | 6 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | AEs leading to dose reduction | 5 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | AEs leading to permanent discontinuation of any study treatment | 1 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | AEs related to study treatment | 7 Participants |
| Multiple Myeloma (MM) | Number of Participants With Adverse Events (AEs) | Any AE | 9 Participants |
Secondary
Overall Survival (OS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time frame: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Survival (OS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | 94.6 Weeks |
Secondary
Overall Survival (OS) in the Anaplastic Thyroid Cancer (ATC) Cohort
Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time frame: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Survival (OS) in the Anaplastic Thyroid Cancer (ATC) Cohort | 62.9 Weeks |
Secondary
Overall Survival (OS) in the Biliary Tract Cancer (BTC) Cohort
Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time frame: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Survival (OS) in the Biliary Tract Cancer (BTC) Cohort | 58.9 Weeks |
Secondary
Overall Survival (OS) in the Hairy Cell Leukemia (HCL) Cohort
Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time frame: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Survival (OS) in the Hairy Cell Leukemia (HCL) Cohort | NA Weeks |
Secondary
Overall Survival (OS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time frame: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Survival (OS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | 76.4 Weeks |
Secondary
Overall Survival (OS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time frame: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Survival (OS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | NA Weeks |
Secondary
Overall Survival (OS) in the Multiple Myeloma (MM) Cohort
Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.
Time frame: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Overall Survival (OS) in the Multiple Myeloma (MM) Cohort | 147.3 Weeks |
Secondary
Progression Free Survival (PFS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort
Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | Investigator assessment | 41.3 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort | Independent radiology review | 40.1 Weeks |
Secondary
Progression Free Survival (PFS) in the Anaplastic Thyroid Cancer (ATC) Cohort
Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Anaplastic Thyroid Cancer (ATC) Cohort | Investigator assessment | 29.1 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Anaplastic Thyroid Cancer (ATC) Cohort | Independent radiology review | 24.1 Weeks |
Secondary
Progression Free Survival (PFS) in the Biliary Tract Cancer (BTC) Cohort
Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Biliary Tract Cancer (BTC) Cohort | Investigator assessment | 39.0 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Biliary Tract Cancer (BTC) Cohort | Independent radiology review | 32.6 Weeks |
Secondary
Progression Free Survival (PFS) in the Hairy Cell Leukemia (HCL) Cohort
Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time frame: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Hairy Cell Leukemia (HCL) Cohort | NA Weeks |
Secondary
Progression Free Survival (PFS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort
Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time frame: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Investigator assessment | 24.0 Weeks |
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort | Independent radiology review | 19.7 Weeks |
Secondary
Progression Free Survival (PFS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort
Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time frame: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - Primary analysis cohort.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Investigator assessment | NA Weeks |
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort | Independent radiology review | 40.1 Weeks |
Secondary
Progression Free Survival (PFS) in the Multiple Myeloma (MM) Cohort
Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.
Time frame: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)
Population: ITT/Evaluable population - primary analysis cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | Progression Free Survival (PFS) in the Multiple Myeloma (MM) Cohort | 27.5 Weeks |
Post Hoc
All Collected Deaths
On-treatment deaths were collected from first dose of study medication to 30 days after study drug discontinuation, for a maximum duration of 85 months. Post-treatment survival follow-up deaths were collected from day 31 after last dose of first dose of study medication, up to 92 months. All deaths refer to the sum of on-treatment deaths and post-treatment survival follow-up deaths.
Time frame: On-treatment deaths: Up to 85 months. Post-treatment survival follow-up deaths: Up to 92 months.
Population: All-treated Subjects (ATS) population - Primary and expansion cohort combined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anaplastic Thyroid Cancer (ATC) | All Collected Deaths | On-treatment deaths | 6 Participants |
| Anaplastic Thyroid Cancer (ATC) | All Collected Deaths | All deaths | 24 Participants |
| Anaplastic Thyroid Cancer (ATC) | All Collected Deaths | Post-treatment survival follow-up deaths | 18 Participants |
| Biliary Tract Cancer (BTC) | All Collected Deaths | All deaths | 34 Participants |
| Biliary Tract Cancer (BTC) | All Collected Deaths | Post-treatment survival follow-up deaths | 28 Participants |
| Biliary Tract Cancer (BTC) | All Collected Deaths | On-treatment deaths | 6 Participants |
| Gastrointestinal Stromal Tumor (GIST) | All Collected Deaths | All deaths | 1 Participants |
| Gastrointestinal Stromal Tumor (GIST) | All Collected Deaths | On-treatment deaths | 0 Participants |
| Gastrointestinal Stromal Tumor (GIST) | All Collected Deaths | Post-treatment survival follow-up deaths | 1 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | All Collected Deaths | On-treatment deaths | 1 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | All Collected Deaths | Post-treatment survival follow-up deaths | 3 Participants |
| Low Grade (WHO G1/G2) Glioma (LGG) | All Collected Deaths | All deaths | 4 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | All Collected Deaths | Post-treatment survival follow-up deaths | 26 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | All Collected Deaths | On-treatment deaths | 2 Participants |
| High Grade (WHO G3/G4) Glioma (HGG) | All Collected Deaths | All deaths | 28 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | All Collected Deaths | Post-treatment survival follow-up deaths | 3 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | All Collected Deaths | On-treatment deaths | 0 Participants |
| Adenocarcinoma of the Small Intestine (ASI) | All Collected Deaths | All deaths | 3 Participants |
| Hairy Cell Leukemia (HCL) | All Collected Deaths | Post-treatment survival follow-up deaths | 4 Participants |
| Hairy Cell Leukemia (HCL) | All Collected Deaths | On-treatment deaths | 4 Participants |
| Hairy Cell Leukemia (HCL) | All Collected Deaths | All deaths | 8 Participants |
| Multiple Myeloma (MM) | All Collected Deaths | On-treatment deaths | 1 Participants |
| Multiple Myeloma (MM) | All Collected Deaths | Post-treatment survival follow-up deaths | 8 Participants |
| Multiple Myeloma (MM) | All Collected Deaths | All deaths | 9 Participants |