MoST Addendum 12 (substudies 27-30): This phase II trial is evaluating how safe and effective a combination of two targeted therapies (vemurafenib and cobimetinib) are in people with metastatic non-squamous non-small cell lung cancer and other solid cancers with BRAF V600 mutationsSingle arm, open label, phase II trial of vemurafenib and cobimetinib in patients with metastatic non-squamous non-small cell lung cancer and other tumours harbouring BRAF V600 mutations detected by comprehensive genomic profiling

Exclusion

1. Known history of hypersensitivity or contraindication to vemurafenib or cobimetinib;
2. History of prior BRAF and/or mitogen-activated protein kinase pathway inhibitor treatment;
3. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s);
a. History of clinically significant cardiac dysfunction, as determined by left ventricular ejection fraction (LVEF) < 40%;
b. QTc > 500 ms on baseline electrocardiogram;
c. Uncorrectable electrolyte abnormalities
d. History of retinal pathology on ophthalmological examination that is considered a risk factor for retinal detachment, retinal vein occlusion, or vascular-related macular degeneration;
e. History of uncontrolled glaucoma with intraocular pressure;
f. Uncontrolled systemic infections;
4. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
5. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment:
a. Radiation therapy, major surgery, or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
b. Any systemic therapy within 28 days prior to the first dose of study treatment;
6. Administration of any investigational treatment within 28 days prior to receiving the first dose of study treatment;
7. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g. hearing loss, peripheral neuropathy);
8. Prior or concurrent malignancy. History of another primary malignancy except for:
a. Malignancy treated with curative intent and with no known active disease within 2 years before consent to molecular screening and of low potential risk for recurrence;
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
c. Adequately treated carcinoma-in-situ without evidence of disease;
d. For participants with treatment-refractory solid tumours, a concurrent or past history of competing malignancy within 2 years, prior to molecular screening registration, is eligible, unless the competing malignancy is expected to lead to a shorter survival than the index BRAFV600-harbouring malignancy. The patient is ineligible if the concurrent malignancy harbours an activating RAS (i.e. KRAS, HRAS, or NRAS) mutation;
9. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or agree to use a highly effective form of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men with partners of childbearing potential must have been surgically sterilised or agree to use a highly effective form of contraception (See Section 15.1 Acceptable Methods of Contraception).