• To evaluate the efficacy of treatment• To evaluate the safety of treatment
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• pRR (defined as the proportion of patients with pCR, pnCR, and pPR) at time
of surgery, as determined by independent pathologic review
Secondary outcome
• pRR (defined as the proportion of patients with pCR, pnCR, and pPR) at time
of surgery, as determined by local pathologic assessment
• EFS, defined as the time from randomization to any of the following events
(whichever occurs first): Disease progression that precludes surgery, as
assessed by the investigator according to RECIST v1.1; local, regional or
distant disease recurrence; or death from any cause
• RFS, defined as the time from surgery to the first documented recurrence of
disease or death from any cause
• OS, defined as the time from randomization to death from any cause
• ORR, defined as the proportion of patients with a CR or PR as determined by
the investigator according to RECIST v1.1, prior to surgery
Responses will be assessed and determined according to RECIST v1.1 but are not
required to be confirmed by later imaging studies.
• Incidence, nature, and severity of adverse events and laboratory
abnormalities, with severity determined according to NCI CTCAE v5.0
CRS severity will also be determined according to the ASTCT CRS Consensus
Grading Scale.
• Incidence and nature of immune-related adverse events Grade * 3 during the
first 12 weeks
• Rate and duration of delayed surgery due to treatment-related adverse events
• Surgical complication rates according to Clavien Dindo surgical
classification after CLND
Background summary
BACKGROUND ON MELANOMA
Melanoma is a malignant tumor of melanocytes. This potentially deadly form of
skin cancer is one of the fastest growing malignancies (Algazi et al. 2010;
Finn et al. 2012). More than 300,000 people worldwide are currently diagnosed
with melanoma each year, and 57,000 people die of the disease (Ferlay et al.
2018). The clinical outcomes of patients with melanoma are highly dependent on
the stage at presentation. When melanoma is diagnosed early (Stage I and II),
it is generally curable with surgery as the treatment of choice, with a long
term survival rate of around 90% for Stage I melanoma (Balch et al. 2009).
However, most people with more advanced melanoma have a poor prognosis (Finn et
al. 2012). Patients with lymph node involvement (Stage III) have a high risk
of local and distant relapse after surgery, and the 5 year survival rate is
32%*93% in this patient group (Gershenwald et al. 2017). Few patients have
metastatic disease (Stage IV) at presentation, but some develop metastases
after their initial definitive treatment. Immunotherapy and targeted therapies
have improved the outcomes of those patients, and the 5 year survival rate is
around 50% (Larkin et al. 2015; Wolchok et al. 2017; Larkin et al. 2019; Robert
et al. 2019; Long et al. 2020). Despite recent therapeutic advances, melanoma
continues to be a serious health issue, with a high medical need and a steadily
increasing incidence over the past 30 years (Bataille 2009).
IMMUNOTHERAPIES
A variety of immunotherapies have been approved for the treatment of melanoma,
and immunotherapy has shown benefit regardless of PD L1 expression or BRAF
mutations.
Three CPIs, namely ipilimumab, pembrolizumab, and nivolumab, are now approved
by the FDA for the treatment of unresectable or advanced disease. Each has
shown improved OS against different comparators. Treatments shown to be
effective in the unresectable or metastatic disease setting have also proven to
be effective adjuvant therapies for patients with resectable Stage III
melanomas. The current standard of care is surgery followed by adjuvant
anti-PD 1 or targeted therapy.
Ipilimumab, a monoclonal antibody targeting CTLA 4, demonstrated significant
improvement in OS in two randomized trials (Hodi et al. 2010; Robert et al.
2011), and was the first CPI approved for use in unresectable or metastatic
melanoma. It was also the first CPI to be approved by the FDA as adjuvant
therapy, and it has demonstrated improved OS at a dose of 10 mg/kg when
compared with placebo in the European Organisation for Research and Treatment
of Cancer 18071 study (Eggermont et al. 2016). The subsequent Intergroup E1609
trial demonstrated better outcomes with low dose (3 mg/kg) ipilimumab; this
dose has been approved for metastatic disease (Tarhini et al. 2020). Anti-PD 1
monotherapy (pembrolizumab or nivolumab) shows improved efficacy outcomes with
better safety profiles compared with treatment using single agent anti-CTLA 4
(ipilimumab) or the investigator*s choice of chemotherapy.
Pembrolizumab was initially approved for the treatment of patients with
advanced or unresectable melanoma who progressed after ipilimumab and/or BRAF
therapy (Ribas et al. 2015a; Robert et al. 2015b). It is now approved for the
treatment of patients with unresectable or metastatic melanoma, as well as for
the adjuvant treatment of patients with melanoma with lymph node involvement
following complete resection.
Nivolumab was originally approved in advanced melanoma patients without BRAF
mutation (Robert et al. 2015a). It is now approved for patients with
unresectable or metastatic melanoma, and for patients with melanoma with lymph
node involvement or metastatic disease who have undergone complete resection in
the adjuvant setting.
The combination of anti-PD 1 and anti-CTLA 4 immunotherapies (nivolumab plus
ipilimumab) further prolonged PFS and OS compared with ipilimumab or nivolumab
alone, and this combination has been approved for previously untreated patients
with unresectable or metastatic melanoma (Larkin et al. 2015). The CheckMate
238 study compared nivolumab with ipilimumab. At a median follow up of 51
months, nivolumab improved RFS and distant metastasis free survival while
reducing toxicity. The OS was similar in the two groups (Ascierto et al. 2020).
NEOADJUVANT IMMUNOTHERAPY
Nonclinical studies demonstrated improved survival and increased anti tumor
immunity when immune CPI therapy was given before surgery as compared with
adjuvant application (Liu et al. 2016; Brockwell et al. 2017;
Bourgeois-Daigneault et al. 2018; Brooks et al. 2018; O*Donnell et al. 2019).
Patients with clinically detectable Stage III melanoma are ideal candidates for
neoadjuvant therapy because they represent a high risk patient population with
poor outcomes when treated with upfront surgery alone. Neoadjuvant therapy
also has the advantage of providing information on pathologic response, which
is valuable to estimate prognosis and to guide the choice of adjuvant therapy
and follow up (Tetzlaff et al. 2018). Moreover, the availability of tumor
tissue before and following therapy enables efficient exploration of possible
mechanisms of resistance and response as well as identification of baseline
biomarkers. Neoadjuvant therapy for melanoma is now an active area of
research, with numerous completed and ongoing trials that have disparate
designs, endpoints, and analyses (Menzies et al. 2021). The International
Neoadjuvant Melanoma Consortium (INMC) was created by experts in medical
oncology, surgical oncology, pathology, radiation oncology, radiology, and
translational research who developed recommendations for investigating
neoadjuvant therapy in melanoma to align future trial designs and correlative
analyses (Amaria et al. 2019).
Six melanoma neoadjuvant trials were conducted recently with BRAF/MEK-targeted
therapy or PD-1-based immunotherapy (reviewed by Amaria et al. 2019). These
trials demonstrated that neoadjuvant therapies can achieve high pathologic
complete response (pCR) rates and impressive RFS in Stage III melanoma (Menzies
et al. 2021; Rozeman et al. 2021). The initial data are particularly promising
for the neoadjuvant combination of nivolumab plus ipilimumab. Treatment with
nivolumab plus ipilimumab results in pathologic response rates (pRRs) between
70%*80%, is well tolerated, and may reduce surgical morbidity (Rozeman et al.
2019; Blank et al. 2020).
This study protocol was developed in accordance with INMC guidelines to create
the needed consistency amongst neoadjuvant trials in order to facilitate
optimal data organization for future regulatory review. Its exploratory
analysis plan will strengthen translational research across the melanoma
disease continuum.
STUDY RATIONALE
This randomized Phase Ib/II umbrella study is designed to accelerate the
development of treatments or treatment combinations by identifying early
signals and establishing proof of concept clinical data in patients with
resectable melanoma. Single agent immune CPIs or targeted therapies, dual CPI
combinations, and CPIs in combination with targeted therapies have shown
promising objective response rates (ORRs) and OS and are approved for use in
patients with melanoma.
Study objective
• To evaluate the efficacy of treatment
• To evaluate the safety of treatment
Study design
Description of the Study
This is a Phase Ib/II, open label, multicenter, randomized, umbrella study in
patients with resectable Stage III (Cohort 1) or Stage IV (Cohort 2) melanoma.
The study is designed with the flexibility to open new treatment arms as new
treatments become available, close existing treatment arms that demonstrate
minimal clinical activity or unacceptable toxicity, modify the patient
population (e.g., with regard to prior anti cancer treatment or biomarker
status), or introduce additional cohorts of patients with other types of
melanoma.
When additional treatment options become available, patients may be eligible to
receive treatment with a different treatment combination in an additional study
stage (Stage 2). When a Stage 2 treatment is available, this will be
introduced by amending the protocol.
Two cohorts will be enrolled in parallel in this study. Cohort 1 will enroll
patients with resectable Stage III melanoma with measurable lymph node
metastases according to Response Evaluation Criteria in Solid Tumors, Version
1.1 (RECIST v1.1) that can be biopsied, who have no history of
intransit-metastases within the last 6 months, and who have not received
systemic CIT for their disease, e.g., PD 1/PD-L1 and/or CTLA-4 blocking agents
or other agents. Cohort 2 will enroll patients with Stage IV melanoma who
experienced disease progression during or after at least one but not more than
two lines of treatment for metastatic disease. Up to two lines of checkpoint
inhibition therapy (monotherapy or combination therapy) are allowed. Patients
with BRAF-mutant disease may have received an additional line of targeted
therapy (either before, intermittent with, or after the checkpoint inhibition
therapy) or may have received targeted therapy and checkpoint inhibition
therapy concurrently as one combination treatment. Patients with BRAF-mutant
melanoma with rapidly progressive disease who have not been previously treated
with approved targeted therapies are not eligible.
Treatment Assignment
In Cohort 1, patients will be randomly assigned to a control arm (nivolumab
plus ipilimumab [Nivo * Ipi]) or an experimental arm consisting of RO7247669,
atezolizumab in combination with tiragolumab (Atezo * Tira), or RO7247669 in
combination with tiragolumab (RO7247669 * Tira). Patients will be stratified
by geographic region (Australia vs. Rest of the World) and baseline LDH (* the
upper limit of normal [ULN] vs. * ULN).
In Cohort 2, patients will be enrolled into an experimental arm consisting of
RO7247669 in combination with tiragolumab (RO7247669 * Tira). Enrollment will
begin with a 6 patient safety run-in phase. Patients from French
investigational sites are excluded from the safety run-in phase and may only be
enrolled into the preliminary phase, which succeeds the safety-run-in.
Approximately 61*191 patients will be enrolled during the study, including
approximately 6 patients who will be enrolled in the safety run-in phase of
Cohort 2. Enrollment within the experimental arms will take place in two
phases: a preliminary phase, followed by an expansion phase. Approximately
15*20 patients will be enrolled in each treatment arm during the preliminary
phase. If clinical activity (pathologic response in Cohort 1) is observed in
an experimental arm during the preliminary phase, approximately 20 additional
patients may be enrolled in that arm during the expansion phase.
The Sponsor may decide to delay or suspend enrollment within a given treatment
arm. Experimental arms with insufficient clinical activity or unacceptable
toxicity will not be expanded. Additional patients may be enrolled to ensure
balance among treatment arms with respect to demographic and baseline
characteristics, including potential predictive biomarkers, in order to enable
further subgroup analyses. New experimental arms may be added during the study
by amending the protocol.
The randomization ratio will depend on the number of experimental arms that are
available (e.g., if an arm is added or enrollment in an arm is suspended,
pending analysis of results from the preliminary phase), with the stipulation
that the likelihood of being allocated to the control arm is no more than 35%.
Randomization will take into account arm-specific exclusion criteria. Patients
will be ineligible for a specific arm if they meet any of the exclusion
criteria outlined for that arm.
Details on the treatment regimens are provided in Table 3.
Intervention
Study Treatments for Cohort 1
1. Nivolumab + ipilimumab (control, CIT combination treatment)
2. RO7247669 (CIT single agent treatment)
3. Atezolizumab + tiragolumab (CIT combination treatment)
4. RO7247669 + tiragolumab (CIT combination treatment)
Study Treatments for Cohort 2
1. RO7247669 + tiragolumab (CIT combination treatment)
Additional CIT treatments or treatment combinations may be added in the future,
and enrollment may be delayed or suspended for some CIT treatments or treatment
combinations. Thus, the number of available CIT treatments or treatment
combinations may increase or decrease over the course of the study. The
control group CIT treatments or treatment combination will be available for
enrollment throughout the study.
Study burden and risks
Screening: Taking part in the screening and treatment assignment procedures for
this study will not cause the patient's health to improve, but the screening
procedures may show that he/she is eligible for the study.
Treatment: The study treatment may improve the patient's condition or bring
him/her to remission, but that is not certain. The skin cancer may come back or
get worse at any time during this study.
In Cohort 1, there is a risk of delaying a potentially curative surgery
(removal of lymph nodes) due to side effects from the study drugs.
In Cohort 2, the patient may be foregoing an approved, standard therapy with
proven survival benefit.
In addition:
- The patient may experience the side effects or adverse effects of the study
treatment, as described in Section 6 of the ICF.
- There may be some discomfort from the measurements during the study, as
described in Section 7 of the ICF.
- Taking part in the study will cost extra time.
- The patients have to comply with the study agreements.
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Listed location countries
Age
Inclusion criteria
Shared Inclusion Criteria for Cohort 1 and Cohort 2 Patients must meet all of
the following criteria to qualify for Cohort 1 and Cohort 2: • Signed Informed
Consent Form • Age >= 18 years at the time of signing Informed Consent Form
• ECOG performance status (PS) of 0 or 1 • Ability to comply with the protocol,
in the investigator*s judgment • Availability of a representative tumor
specimen that is suitable for biomarker testing via central laboratory Baseline
tumor tissue samples will be collected from all patients (except patients in
the Cohort 2 safety run-in phase) by biopsy of a metastatic lymph node (Cohort
1) or other metastatic lesion (Cohort 2) at screening. In addition, archival
primary tumor tissue will be submitted from all patients if available. In case
no archival primary tissue is available (e.g., for patients with unknown
primary tumor), enrollment is permitted. For archival tissue, a formalin-fixed,
paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) with
sufficient size and tumor content representation, preferably including the
invasive margin, or if available at least 16 slides containing unstained,
freshly cut, serial sections must be submitted along with an associated
pathology report. • Adequate hematologic and end-organ function, defined by the
following laboratory test results, obtained within 14 days prior to initiation
of study treatment: - ANC >= 1.5 x 109/L (1500/uL) - Lymphocyte count >=
0.5 x 109 cells/L (500/uL) Borderline machine lymphocyte counts may be
confirmed by a manual count. - Platelet count >= 100 x 109/L (100,000/uL) -
Hemoglobin >= 90 g/L (9 g/dL) - AST, ALT, and ALP <= 2.5 x ULN with the
following exceptions: For Cohort 2, patients with documented liver metastases:
AST and ALT <= 5 x ULN. For Cohort 2, patients with documented liver or bone
metastasis: ALP <= 5 x ULN. - Total bilirubin <= 1.5 x ULN, with the
following exception: Patients with known Gilbert disease: bilirubin level <=
3 x ULN - Creatinine <=1.5 x ULN or creatinine clearance >= 30 mL/min
(calculated using the Cockcroft-Gault formula) - Serum albumin >= 25 g/L
(2.5 g/dL) - For patients not receiving therapeutic anticoagulation: INR and
aPTT <= 1.5 x ULN • For patients receiving therapeutic anticoagulation:
stable anticoagulant regimen (i.e., no new thrombosis, thromboembolic event, or
bleeding episode within 3 months prior to study treatment start) • Negative HIV
test at screening with the following exception: Patients with a positive HIV
test at screening are eligible provided they are stable on anti-retroviral
therapy, have a CD4 count >= 200/uL, and have an undetectable viral load.
Patients without a prior positive HIV test result will undergo an HIV test at
screening, unless not permitted per local regulations. • Negative hepatitis B
surface antibody (HBsAb) and negative total hepatitis B core antibody (HBcAb)
test at screening. If a patient has a negative hepatitis B surface antigen
(HBsAg) test and a positive total HBcAb test at screening, a hepatitis B virus
(HBV) DNA test must also be performed to rule out active HBV. • Negative
hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
test followed by a negative HCV RNA test at screening The HCV RNA test will be
performed only for patients who have a positive HCV antibody test. • For women
of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures • For men: agreement to
remain abstinent (refrain from heterosexual intercourse) or use contraceptive
measures, and agreement to refrain from donating sperm Inclusion Criteria for
Cohort 1 Patients must meet all of the following criteria to qualify for Cohort
1: • Histologically confirmed resectable Stage III melanoma (T: T0, Tx, or
T-14; N: cN1-3, pN1b/2b/3b; M: M0 according to AJCC-8) and no history of
in-transit metastases within the last 6 months Patients may present with
primary melanoma with concurrent regional nodal metastasis, or a history of
primary melanoma or unknown primary melanoma with clinically detected regional
nodal recurrence, and may belong to any of the following groups: - Primary
cutaneous melanoma with concurrent clinically/radiologically apparent regional
lymph node metastases - Clinically/radiologically detected recurrent melanoma
at the proximal regional lymph node(s) basin - Clinically/radiologically
detected nodal melanoma (if single site) arising from an unknown primary • Fit
and planned for CLND (as assessed by surgeon prior to randomization according
to local guidelines) • Measurable disease (at least one target lesion)
according to RECIST v1.1 At least one macroscopic lymph node metastasis
(measurable according to RECIST v1.1) to be biopsied. Inclusion Criteria for
Cohort 2 Patients must meet all of the following criteria to qualify for Cohort
2: • Life expectancy >= 3 months, as determined by the investigator •
Histologically confirmed Stage IV (metastatic) cutaneous melanoma according to
AJCC-8 • Disease progression during or following at least one but no more than
two lines of treatment for metastatic disease Up to two lines of checkpoint
inhibition therapy (monotherapy or combination therapy) are allowed. Patients
with BRAF-mutant disease may have received an additional line of targeted
therapy (either before, intermittent with, or after the checkpoint inhibition
therapy), or may have received targeted therapy and checkpoint inhibition
therapy concurrently as one combination treatment. Patients with BRAF-mutant
melanoma with rapidly progressive disease who have not been previously treated
with approved targeted therapies are not eligible. Patients who received
adjuvant treatment with checkpoint inhibition therapy for localized melanoma
require an additional line of checkpoint inhibition therapy in the metastatic
setting. Patients who relapse or systemically progress during or within 6
months of completion of adjuvant therapy are eligible and do not require an
additional line of checkpoint inhibition therapy. • Measurable disease (at
least one target lesion) according to RECIST v1.1 At least one metastasis
(measurable according to RECIST v1.1).
Exclusion criteria
Exclusion Criteria for Cohort 1 and Cohort 2 Patients who meet any of the
following criteria will be excluded from study entry: • Mucosal and uveal
melanoma Acral lentiginous melanoma is excluded for Cohort 1. For Cohort 2,
acral lentiginous melanoma is permitted; however, the proportion of patients
should not exceed 20% of response-evaluable patients. • Treatment with
investigational therapy within 28 days prior to initiation of study treatment •
Treatment with systemic immunostimulatory agents (including, but not limited
to, interferon [IFN] and interleukin [IL]-2) within 4 weeks or 5
drug-elimination half-lives (whichever is longer) prior to initiation of study
treatment • Prior allogeneic stem cell or solid organ transplantation • Known
immunodeficiency or conditions requiring treatment with systemic
immunosuppressive medication (including, but not limited to, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor**
agents), or anticipation of need for systemic immunosuppressant medication
during study treatment, with the following exceptions: Patients on replacement
doses of corticosteroids to manage hypopituitary or adrenal insufficiency are
eligible for the study. Patients who received acute, low-dose, systemic
immunosuppressant medications, or a one-time pulse dose of systemic
immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast
allergy) are eligible for the study. Patients requiring chronic low-dose
systemic corticosteroid treatment (i.e., a maximal dose of corticosteroids <=
10mg/day equivalent prednisone) are eligible. Patients who received
mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic
obstructive pulmonary disease or asthma, or low-dose corticosteroids for
orthostatic hypotension or adrenal insufficiency are eligible for the study. •
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of
study treatment, or anticipation of need for such a vaccine during study
treatment or within 5 months after the final dose of study treatment • Active
or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease,
antiphospholipid antibody syndrome, Wegener granulomatosis, Sjo*gren syndrome,
Guillain-Barre* syndrome, or multiple sclerosis, with the following exceptions:
Patients with a history of autoimmune-related hypothyroidism who are on
thyroid-replacement hormone are eligible for the study. Patients with
controlled Type 1 diabetes mellitus who are on a stable insulin regimen are
eligible for the study. Patients with eczema, psoriasis, lichen simplex
chronicus, or vitiligo with dermatologic manifestations only (e.g., patients
with psoriatic arthritis are excluded) are eligible for the study provided all
of following conditions are met: - Rash must cover < 10% of body surface
area. - Disease is well controlled at baseline and requires only low-potency
topical corticosteroids. - There is no occurrence of acute exacerbations of the
underlying condition requiring psoralen plus ultraviolet A radiation,
methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or
high-potency or oral corticosteroids within the previous 12 months. • History
of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence
of active pneumonitis on screening chest computed tomography (CT) scan.
Patients with a history of CIT-related pneumonitis Grade < 2 are eligible. •
History of malignancy other than malignant melanoma within 2 years prior to
screening, with the exception of malignancies with a negligible risk of
metastasis or death (e.g., 5-year overall survival [OS] rate > 90%), such as
adequately treated carcinoma in situ of the cervix, non melanoma skin
carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I
uterine cancer • Active tuberculosis (TB) • Severe infection within 4 weeks
prior to initiation of study treatment, including, but not limited to,
hospitalization for complications of infection, bacteremia, or severe
pneumonia, or any active infection that, in the opinion of the investigator,
could impact patient safety • Treatment with therapeutic or prophylactic oral
or IV antibiotics within 2 weeks prior to initiation of study treatment •
Significant cardiovascular disease such as New York Heart Association cardiac
disease (Class II or greater), myocardial infarction or cerebrovascular
accident within 3 months prior to initiation of study treatment, unstable
arrhythmia, or unstable angina • Uncontrolled hypertension (defined as resting
systolic blood pressure * 150 mmHg and/or diastolic blood pressure > 100
mmHg in two or more serial measurements) • Major surgical procedure, other than
for diagnosis, within 4 weeks prior to initiation of study treatment, or
anticipation of need for a major surgical procedure other than CLND, during the
study Placement of central venous access catheter (e.g., port or similar) is
not considered a major surgical procedure and is therefore permitted. • Any
other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may
affect the interpretation of the results, impair the ability of the patient to
participate in the study, or may render the patient at high risk from treatment
complications • History of severe allergic reactions to chimeric or humanized
antibodies or fusion proteins • Known hypersensitivity to Chinese hamster ovary
cell products or recombinant human antibodies • Known allergy or
hypersensitivity to any of the study drugs or their excipients • Known
intolerance to any of the drugs required for premedication (acetaminophen,
ranitidine, diphenhydramine, and methylprednisolone) • Pregnancy or
breastfeeding, or intention of becoming pregnant during the study Women of
childbearing potential must have a negative serum pregnancy test result within
14 days prior to initiation of study treatment. • Eligible only for the control
arm Exclusion Criteria for Cohort 1 Patients who meet any of the following
criteria will be excluded from Cohort 1: • Distantly metastasized melanoma •
History of in-transit metastases within the last 6 months • Prior radiotherapy
• Prior immunotherapy, including anti-CTLA-4, anti-PD-1, and anti-PD-L1
therapeutic antibodies, and other systemic therapy for melanoma Exclusion
Criteria for Cohort 2 Patients who meet any of the following criteria will be
excluded from Cohort 2: • Symptomatic, untreated, or progressing CNS metastases
Asymptomatic patients with treated CNS lesions are eligible, provided that all
of the following criteria are met: - Measurable disease, per RECIST v1.1, must
be present outside the CNS. - The patient has no history of intracranial
hemorrhage or spinal cord hemorrhage. - CNS metastases are stable for >= 4
weeks prior to initiation of study, or neurosurgical resection occurred >=
28 days prior to initiation of study treatment. - The patient has no
requirement for corticosteroids as therapy for CNS disease for at least 14 days
prior to initiation of study treatment. - Anti-convulsant therapy at a stable
dose is permitted. • Active or history of carcinomatous
meningitis/leptomeningeal disease • Uncontrolled tumor-related pain Patients
requiring pain medication must be on a stable regimen at screening. Symptomatic
lesions (e.g., bone metastases or metastases causing nerve impingement)
amenable t
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-002147-29-NL |
| CCMO | NL78989.056.21 |