Subprotocol Z1C eligibility (in addition to master):
-Patients must have CDK4 amplification or CDK6 amplification and tumor Rb protein expression by immunohistochemistry as determined by the MATCH screening assessment
-Patients must not have breast cancer, mantle cell lymphoma, myeloma, or liposarcoma
-Patients must not have received prior therapy with a CDK4 or CDK6 inhibitor

Subprotocol Z1D eligibility (in addition to master eligibility):
-Patients must have mismatch repair deficiency as determined by the MATCH screening assessment.
-No prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 or anti-CTLA-4 antibodies (or any other antibody targeting T cell co-regulatory pathways).
-Patients with colorectal cancer are excluded.
-Must not have received any of the following therapies within four weeks prior to the first dose of the study drug: IL-2, interferon, or other non-study immunotherapy regimens or immunosuppressive agents.The master protocol eligibility criterion regarding wash-out period from prior therapy is also applicable.
-Must not have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration. Use of such agents while on study is also prohibited.
-Must not have a history of any autoimmune disease
-Must not be on supplemental home oxygen.
-Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) within 14 days of study drug administration.

Subprotocol Z1E eligibility (in addition to master):
-Patients must have a malignancy harboring an NTRK1, NTRK2 or NTRK3 gene fusion, as determined by the MATCH screening assessment
-Patients who have previously received treatment with a TRKA, TRKB, or TRKC inhibitor are excluded.

-Patients must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master Protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7).
-Patients must have PIK3CA mutation as determined via the MATCH Master Protocol and described in Appendix I.
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG

- Patients must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition.
-Patients must not have had prior therapy with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors.
-Patients must not have activating KRAS mutations.
-Patients must not have HER2 positive (3+ by IHC or FISH ratio ? 2) breast cancer.
-Patients must not have indolent NHL (follicular lymphoma, SLL/CLL, LPL, marginal zone lymphoma) or DLBCL (diffuse large B cell lymphoma).
-Patients must not be on strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and for the duration of study treatment.

Patients must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master Protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7).
-Patients must have complete loss of cytoplasmic and nuclear PTEN by immunohistochemistry as determined via the MATCH Master Protocol and described in Appendix I. Patients can have any PTEN mutation or deletion status, but MUST have PTEN loss by IHC.
-Patients must not have co-existing aberrations in the MAPK or PI3K/MTOR pathways as determined by the MATCH screening assessment in NRAS, HRAS, KRAS, BRAF, PIK3CA, AKT or mTOR.
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important

abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
-Patients must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition.
-Patients must not have had prior treatment with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors.
-Patients must not be on strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and for the duration of study treatment.
-Patients must not have uncontrolled hypertension defined as SBP greater than 160 mmHg or diastolic BP greater than 100 mmHg or use of more than 2 anti-hypertensive medications.

-Patients must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master Protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7).
-Patients must have mutations in the PTEN

gene with 1% or more expression of PTEN by IHC as determined via the MATCH Master Protocol and as described in Appendix I.
-Patients must not have co-existing aberrations in the MAPK or PI3K/MTOR pathways as determined by the MATCH screening assessment in NRAS, HRAS, KRAS, BRAF, PIK3CA, AKT or mTOR.

-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG

-Patients must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition.

-Patients must not require prior treatment with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors.

Patients must not be on strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and for the duration of study treatment.

-Patients must not be on anti-arrhythmic therapy other than digoxin or beta-blockers.

Subprotocol Z1I eligibility (in addition to master):
-Patients must have mutation in the BRCA1 or BRCA2 gene in the tumor as determined by the MATCH screening assessment.

Patients with tumor carrying mutations defined as variants of uncertain significance will not qualify
-Patients with ovarian cancer must have received a PARP inhibitor as part of or as one of their prior lines of therapy
-Resting corrected QTc interval using the Fridericia formula (QTcF) should be < 450 msec/male and < 470 msec/female

-Patients must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master Protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7).
-Patients must have an AKT mutation as determined via the MATCH Master Protocol and described in Appendix II. See Appendix II for information on the AKT mutation and corresponding Levels of
Evidence.

-Patients with hormone receptor positive, defined as estrogen receptor and/or progesterone receptor > 1% by immunohistochemistry19, AND HER2 negative unresectable breast cancer, with no overexpression by IHC or amplification by in-situ hybridization20, are allowed to continue fulvestrant or an aromatase inhibitor (anastrazole, letrozole, exemestane) with Ipatasertib if patient just progressed on this antiestrogen therapy. GnRH agonists (such as leuprolide or goserelin) are
allowed.

- Patients with castration-resistant prostate cancer should maintain castrate levels of testosterone (i.e., with GnRH agonists or through surgical castration).
-Patients must not have known hypersensitivity to Ipatasertib or compounds of similar chemical or biologic composition.
-Patients with known KRAS, NRAS, HRAS, or BRAF mutations are not eligible for this protocol, as these mutations may lead to limited response due to resistance.
-Patients with diabetes or risk for hyperglycemia are eligible. Patients with diabetes mellitus should be on a stable dose of oral hypoglycemic agents for ? 4 weeks and appropriate diet.
-Prior PI3K and mTOR inhibitors are allowed, including in the metastatic setting
-Patients with a history of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) or active diverticulitis are not eligible.

- Patients may not have received strong inhibitors or potent inducers or substrates of CYP3A4/5 within 2 weeks before the first dose of study treatment (3 weeks for St John’s Wort).

-Patients must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master Protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7).
-Patients must have a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration, as determined via the MATCH Master Protocol and according to Appendix II.

- Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG
-Patients must not have known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to BVD-523FB (ulixertinib), dimethyl sulfoxide (DMSO), or excipients.
-Patients must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN) or < 50% (whichever is higher).
-Patients must not have prior use of MEK or ERK 1/2 inhibitors.

-Patients must not have a history of RVO or central serous retinopathy. Patients with visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis or central serous retinopathy will be excluded.
-Intraocular pressure is ? 21mm Hg as measured by tonography. Patients diagnosed with glaucoma within 1 month prior to Step 1 Registration are excluded.

-Patients must not have leptomeningeal metastases or spinal cord compression due to disease.
-Patients must not have primary malignancy of the central nervous system.