Inclusion Criteria:

          -  Provision of written informed consent

          -  Ability of patient to understand and comply with the protocol for the duration of the
             study, including treatment and scheduled visits and examinations

          -  Diagnosis of a metastatic or locally advanced malignancy

          -  Progressive disease

          -  At least one measurable lesion that can be accurately assessed at baseline by computed
             tomography or magnetic resonance imaging and is suitable for repeated assessment

          -  Prior administration of at least one standard chemotherapy for primary and/or relapsed
             malignancy according to current guidelines

          -  ECOG Performance Status ≤2

          -  Age ≥18 years, no upper age limit

          -  Postmenopausal or evidence of non-childbearing status.

          -  Female patients of childbearing potential and male patients with partners of
             childbearing potential who are sexually active must agree to the use of two highly
             effective forms of contraception. These should be started immediately after signing
             the informed consent form and continued throughout the period of study treatment plus
             three months for female and for male patients thereafter.

          -  Availibility of complete information about the last medical treatment given before
             study participation, i.e. remission status before start of treatment, dosage and
             timing of drugs applicated, remission status and date of progression after treatment
             (in order to calculate PFS 1)

          -  For patients included on the basis of molecular testing other than NCT/DKTK MASTER and
             for patients with an analysis in NCT/DKTK MASTER performed more than 3 months (date of
             tissue sampling) before planned study inclusion, a new tumor biopsy before start of
             study treatment is mandatory. However, patients may be included in the trial with
             archival tissue not older than 3 months on the basis of a case by case discussion with
             the PI.

        Arm-specific Inclusion Criteria as determined by Whole Genome Sequencing and RNA Sequencing
        in NCT/DKTK MASTER or identification by gene panel performed in a certified lab Eligibility
        for the trial and the respective trial arms will be evaluated and determined exclusively by
        the NCT/DKTK molecular tumor board on the basis of results from NCT/DKTK MASTER (for all
        arms) or of results from other molecular studies, e.g. gene panel testing, performed in a
        certified laboratory (for arms 1-6). Trial participation is only possible with a report of
        the NCT/DKTK MASTER MTB confirming trial eligibility.

          -  Arm 1 (BRAF V600E/K): BRAF V600E/K mutation

          -  Arm 2 (ERBB2): ERBB2 amplification/overexpression, activating ERBB2 mutation

          -  Arm 3 (ALK): ALK rearrangement or activating ALK mutations including alternative
             transcription initiation (ALK-ATI) or RET-fusions

          -  Arm 4 (PI3K-AKT): Activating PIK3CA or AKT mutations; other aberrations predicting
             increased PI3K-AKT pathway activity, e.g. PTEN loss

          -  Arm 5: (PI3K-AKT-TAX): Activating PIK3CA or AKT mutations; other aberrations
             predicting increased PI3K-AKT pathway activity, e.g. PTEN lossa

          -  Arm 6 (MAPK): Aberrations other than BRAF V600E/K predicting increased RAF-MEK- ERK
             pathway activity

          -  Arm 7 (Immune evasion): High tumor mutational burden and/or specific alterations
             predicting sensitivity to PD1/PDL1 inhibition (e.g. DNA mismatch repair deficiency or
             PDL1 amplification and/or overexpression), ineligibility for the six specific arms

        Exclusion Criteria (general):

          -  Other malignancy except for study indication within the last 5 years except:
             adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the
             cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or
             other malignancies curatively treated with no evidence of disease for ≥5 years

          -  Concurrent or previous treatment within 30 days prior to C1D1 in another
             interventional clinical trial with an investigational anticancer therapy

          -  Persistent toxicity (≥Grade 2 according to Common Terminology Criteria for Adverse
             Events (CTCAE) version 5.0) caused by previous cancer therapy, excluding alopecia

          -  Clinical signs of active infection (>Grade 2 according to CTCAE version 5.0)

          -  History of human immunodeficiency virus (HIV) infection and immunocompromised patients

          -  Active Hepatitis A virus infection

          -  Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B
             surface antigen (HBsAg) test at baseline patients with a past or resolved HBV
             infection, defined as having a negative HBsAg test and a positive total hepatitis B
             core antibody (HBcAb) test at baseline , are eligible for the study if active HBV
             infection is ruled out on the basis of HBV DNA viral load per local guidelines

          -  Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody
             test at baseline confirmed by a polymerase chain reaction (PCR) positive for HCV RNA
             Dementia or significant impairment of cognitive state

          -  Epilepsy requiring pharmacologic treatment

          -  Pregnancy or breastfeeding

          -  Inability to take oral medication orgastrointestinal disorders likely to interfere
             with absorption of the study medication

          -  Major surgery within four weeks of starting study treatment

          -  Systemic chemotherapy or radiotherapy within two weeks prior to start of study
             treatment or a longer period depending on the characteristics of the agents used (at
             least five-half lives)

          -  Heart failure New York Heart Association (NYHA) II/III/IV

          -  Severe obstructive or restrictive ventilation disorder

          -  Prior allogeneic bone marrow transplantation or solid organ transplant.

          -  Administration of a live, attenuated vaccine within 4 weeks before initiation of study
             treatment or anticipation that such a live attenuated vaccine will be required during
             the study

          -  Patients with clinical suspicion of active tuberculosis

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug

          -  Is taking or requiring the continued use of any of the prohibited concomitant
             medications listed in 5.10

          -  Any concurrent antineoplastic therapy.

          -  Known suspected active alcohol or drug abuse

          -  Hematological malignancies and primary brain tumors. Patients with known progressive
             brain metastases determined by serial imaging or declining neurologic function in the
             opinion of the treating physician are not eligible. Patients with symptomatic
             uncontrolled brain metastases and patients with symptomatic uncontrolled spinal cord
             compression are not eligible. Patients with previously treated brain metastases are
             eligible, provided that the patient has not experienced a seizure or had a clinically
             significant change in neurological status within the three months prior to enrollment.
             All patients with previously treated brain metastases must be clinically stable for at
             least 1 month after completion of treatment and off steroid treatment for one month,
             both prior to study enrolment. Patients with asymptomatic untreated CNS disease may be
             enrolled, provided all of the following criteria are met:

               -  Evaluable or measurable disease outside the CNS

               -  No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm
                  of the optic apparatus (optic nerves and chiasm)

               -  No history of intracranial hemorrhage or spinal cord haemorrhage

               -  No ongoing requirement for dexamethasone for CNS disease; patients on a stable
                  dose of anticonvulsants are permitted

          -  Immune disease as specified below (relevant for all patients at Baseline except arm 3
             (Alectinib))

               -  History of autoimmune disease, including but not limited to myasthenia gravis,
                  myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
                  arthritis, inflammatory bowel disease, vascular thrombosis associated with
                  antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome,
                  Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis;
                  autoimmune-related hypothyroidism (patients on a stable dose of thyroid
                  replacement hormone are eligible for this study) and type I diabetes mellitus
                  (patients on a stable dose of insulin regimen are eligible for this study).

               -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,
                  bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or
                  active pneumonitis; history of radiation pneumonitis in the radiation field
                  (fibrosis) is permitted.

               -  Psoriatic arthritis (however, patients with eczema, psoriasis, lichen simplex
                  chronicus, or vitiligo with dermatologic manifestations only are permitted
                  provided that they meet the following conditions:

               -  Rash must cover less than 10% of body surface area (BSA)

               -  Disease is well controlled at baseline and only requiring low potency topical
                  steroids

               -  No acute exacerbations of underlying condition within the previous 12 months (not
                  requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids,
                  biologic agents, oral calcineurin inhibitors, high potency or oral steroids]).