Clinical Trial Finder

Inclusion Criteria:

• - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol.

• - Patient's tumor must have activating HER2 mutation, as determined via the MATCH Master Protocol.

• - Additionally, any in-frame insertions in exon 20 will be considered an activating mutation.

• - 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 with known left ventricular dysfunction must have echocardiogram (ECHO) or a nuclear study (multiple-gated acquisition [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN).

If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible.

• - NOTE: Pre-treatment LVEF determination in patients without known left ventricular dysfunction is NOT otherwise required.

• - Patients must have =< grade 1 diarrhea at baseline.

• - Patients must have =< grade 1 renal function as defined below: - Creatinine =< 1.5 x normal institutional limits OR.

• - Measured creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal or as calculated by the Cockcroft-Gault equation.

• - This should be strictly followed and will override the MATCH Master Protocol requirements.

Exclusion Criteria:

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

• - Patients with a history of interstitial lung disease will be excluded.

• - Patients must not have had prior treatment with any of the following tyrosine kinase inhibitors (TKIs), which have known activity against HER2 kinase: - Neratinib.

• - AC-480 (BMS-599626) - AST 1306.

• - Canertinib (CI 1033) - CUDC-101.

• - Lapatinib.

• - TAK285.

• - Afatinib.

• - AEE 788.

• - AZD8931.

• - CP-724714.

• - Dacomitinib.

• - Pelitinib.

- Patients with non-small cell lung cancer will be excluded

PRIMARY OBJECTIVE:

• I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

• I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

• II. To evaluate time until death or disease progression.

• III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

• IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE: Patients receive afatinib dimaleate (afatinib) orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Arms

Experimental: Treatment (afatinib dimaleate)

Patients receive afatinib dimaleate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - Afatinib Dimaleate

Given PO