A large, international study in advanced wild-type melanoma looking at the efficacy and safety with cobimetinib (targeted therapy) plus atezolizumab (immunotherapy) compared to pembrolizumab (immunotherapy) where the assigned drug therapy will be known by the patient and investigator.

Phase 1

• Conditions: Metastatic BRAFV600 wild-type melanoma; MedDRA version: 20.0Level: PTClassification code 10040808Term: Skin cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004387-18-IT
• Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-01-20
• Last Update Posted: 24 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 446

Inclusion Criteria

Disease-Specific Inclusion Criteria
• Histologically confirmed locally advanced and unresectable or metastatic melanoma
• Naive to prior systemic anti-cancer therapy for melanoma
• Documentation of BRAFV600 wild-type status in melanoma tumor
tissue through use of a clinical mutation test approved by the local
health authority - A representative, formalin-fixed, paraffin-embedded (FFPE) tumor
specimen in a paraffin block (preferred) or 20 slides containing
unstained, freshly cut, serial sections must be submitted along with an
associated pathology report prior to study entry. If 20 slides are not
available or the tissue block is not of sufficient size, the patient may still
be eligible for the study, after discussion with and approval by the
Medical Monitor.
• Measureable disease according to RECIST v1.1
General Inclusion Criteria
• Age >=18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol, in the investigator's
judgment
• Histologically or cytologically confirmed BRAFV600 wild-type
melanoma
• ECOG Performance Status of 0 or 1
• Life expectancy >=3 months
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use at least two forms of effective contraceptive with a failure rate of < 1% per year during the
treatment period and for at least 3 months after the last dose of cobimetinib and at least 5 months after the last dose of atezolizumab or pembrolizumab after the last dose of cobimetinib and atezolizumab, respectively. Women must refrain from donating eggs during this same
period.
• For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures (e.g. condom), and
agreement to refrain from donating sperm, for at least 3 months after
the last dose of cobimetinib
• Willingness and ability of patients to report selected study outcomes using an electronic device or paper backup questionnaires
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170

Exclusion Criteria

General Exclusion Criteria
- Inability to swallow medications
- Malabsorption condition that would alter the absorption of orally
administered medications
- Pregnancy, breastfeeding, or intention of becoming pregnant during
the study
- History of severe hypersensitivity reactions to components of the cobimetinib, atezolizumab or pembrolizumab, or ipilimumab formulations
- Administration of a live, attenuated vaccine within 4 weeks before
randomization or anticipation of need for such a vaccine during the study
- Any anti-cancer therapy, including chemotherapy or hormonal
therapy, within 2 weeks prior to initiation of study treatment
- Treatment with systemic immunostimulatory agents within 28 days
or 5 half-lives of the drug, whichever is shorter, prior to Day 1 of Cycle 1
- Treatment with systemic immunosuppressive medications within 2
weeks prior to Day 1 of Cycle 1
- Any serious medical condition or abnormality in clinical laboratory
tests that, in the investigator's judgment, precludes the patient's safe
participation in and completion of the study
Cancer-Related Exclusion Criteria
- Ocular melanoma
- Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1
or anticipation of needing such procedure while receiving study
treatment
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
- Active or untreated CNS metastases
Exclusions Related to Cardiovascular Disease
- Unstable angina, new-onset angina within the last 3 months, myocardial infarction within the last 6 months prior to Day 1 of Cycle 1, or current
congestive heart failure classified as New York Heart Association Class II
or higher
- LVEF below institutional lower limit of normal or <50%, whichever is
lower
- Poorly controlled hypertension, defined as sustained, uncontrolled,
non-episodic baseline hypertension consistently above 159/99 mmHg
despite optimal medical management
- History or presence of an abnormal ECG that is clinically significant in
the investigator's opinion, including complete left bundle branch block,
second- or third degree heart block, or evidence of prior myocardial
infarction
Exclusions Related to Infections
- HIV infection
- Active tuberculosis infection
- Severe infections within 4 weeks prior to Day 1 of Cycle 1, including,
but not limited to, hospitalization for complications of infection,
bacteremia, or severe pneumonia
- Signs or symptoms of clinically relevant infection within 2 weeks
prior to Day 1 of Cycle 1
- Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of
Cycle 1
- Active or chronic viral hepatitis B or C infection
Exclusions Related to Ocular Disease
- Known risk factors for ocular toxicity
Exclusions Related to Autoimmune Conditions and Immunomodulatory
Drugs
- Active or history of autoimmune disease or immune deficiency
- Prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, organizing pneumonia, druginduced
or idiopathic pneumonitis, or evidence of active pneumonitis on
screening chest CT scan
- Treatment with systemic immunosuppressive medications within 2
weeks prior to Day 1, Cycle 1
Exclusions Related to Other Medical Conditions or Medications
- Active malignancy (other than melanoma) or a prior malignancy
within the past 3 years
- Any Grade >=3 hemorrhage or bleeding event within 28 days of Day
1 of Cycle 1
- History of stroke, reversible ischem

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified