Summary of significant changes included the following: 1. Part 1 of the study was modified to make premedication mandatory prior to each dose of Sym015. Part 2 of the study was modified to make premedication mandatory prior to each dose of Sym015 during Cycle 1. 2. Definition of dose-limiting toxicities was modified. 3. Protocol was modified to discontinue therapy for all patients who met Hy’s Law criteria that could not be explained by factors not related to Sym015. 4. Additional criteria included for dose reduction due to toxicity. 5. Allowed GnRH analogues in patients with prostate cancer.

Summary of significant changes included the following: 1. Part 1 of the study was modified to make KRAS mutation testing mandatory to include only patients with KRAS WT solid tumor malignancies.

Summary of significant changes included the following: 1. Inclusion criteria No. 6 was modified to require KRAS mutation testing according to institutional standards in order to utilize the various testing platforms that were available at the participating study sites. 2. Part 1 of the study was modified to include a tumor biopsy during screening for assessment of KRAS mutational status, if necessary, for eligibility assessment. 3. Part 2 of the study was modified to include an ADA sample time point at C2/D1. 4. It was clarified that AEs/SAEs were reported from signing of informed consent for participation in the study. Furthermore, it was clarified that patients who signed informed consent and were subsequently considered to be screening failures were followed for AEs/SAEs until it was determined that they were not to be participating in the study. 5. Reporting requirements for safety data to Sponsor or designee were explained. 6. It was made clear that the sample size considerations were based on a 2-stage design, not a 2-stage Minmax design

Summary of significant changes included the following: 1. The overall study design was modified by moving the Q3W Cohort from Part 1 to Part 2 to ensure patients with MET-amplification were treated in this Cohort and thereby introducing a Q2W Basket Cohort as well as a Q3W Basket Cohort in Part 2. 2. Study objectives, study endpoints and patient numbers were updated according to the change in overall study design. 3. 6-12 patients were allowed to be included in the Q3W Basket Cohort. 4. The selection of the Q2W RP2D was confirmed as 18 mg/kg loading dose infused over 1.5 hours on C1/D1 followed by Q2W maintenance doses of 12 mg/kg infused over 1 hour beginning on C1/D15. 5. The select inclusion criterion was modified. 6. The select exclusion criterion was modified and/or deleted. 7. It was clarified that a study site may choose to pre-screen patients utilizing archival tumor tissue to confirm MET-amplification status and/or KRAS mutational status before entering patients into screening for the treatment portion of the study. 8. The infusion time of Sym015 was modified to 1.5 hour (+10 minutes) for doses ≥ 18 mg/kg 9. Preference was made clear for the eligibility assessment for MET-amplification be done using tissue from a tumor biopsy. 10. Skin biopsies were removed from Part 2 of the study. 11. Dose-delay criteria 4 was updated. 12. One of the dose-limiting toxicities (2) was clarified. 13. Dose-reduction criteria 2 and 5 was updated in accordance with dose-limiting toxicity criteria. 14. Overall survival (OS) status was updated in the continued follow-up after the 1M FUP Visit and adjusted the follow-up schedule to be every 2 months. 15. It was updated that PD was not to be captured as an AEs unless the nature of the PD was different than expected. 16. Timelines for reporting of SAE Follow-up information was updated. 17. It was updated that the sample size determination to be based on a Simon’s Optimal 2-stage design.

Summary of significant changes included the following: 1. Inclusion criterion #5 was modified to clarify that patients must have had recurrent and/or PD and were without other therapeutic options. 2. Inclusion criterion #7 was revised to allow local assessment of KRAS-mutation and MET-amplification based on a peripheral blood sample (liquid biopsy). 3. Inclusion and exclusion criteria were modified to allow a subset of patients pretreated with a MET-targeting TKI. 4. It was specified that patients included based on MET-amplification from a liquid biopsy were withdrawn if subsequent analysis of a tumor biopsy did not meet eligibility criteria, and the patients did not have clinical benefit from therapy. Such patients were replaced. 5. The option for investigators was added to include an H2 antagonist and/or acetaminophen premedication, where indicated. 6. Prohibited medication section was modified to allow steroid therapy as prophylaxis for contrast reactions. 7. Other minor updates and clarifications were included.

Summary of significant changes included the following: 1. The overall study design was modified by removing Q3W dosing with Sym015, which was not to be evaluated, and a separate Cohort of KRAS WT, advanced NSCLC patients with METEx14 mutation was added. 2. Secondary study objectives were updated according to the change in overall study design. 3. The summary of clinical findings was updated based on the 7 MET-amplified patients that had been enrolled in the ongoing Part 2 Basket Cohort at the time of the amendment. 4. Inclusion and exclusion criteria were modified to allow enrolment of patients with NSCLC and other malignancies with METEx14 mutation, and who had been pre-treated with MET-targeting TKI. 5. Exclusion criteria was modified to specify time required between prior antineoplastic agent and C1/D1, and prior immunosuppressive or systemic hormonal therapy. 6. Prohibited medication was modified to specify when the use of steroid therapy was considered not allowed. 7. The order of collection of tumor biopsy and biomarker blood sample was specified if collected at the same time point. 8. Other minor updates and clarifications were included

Summary of significant changes included the following: 1. Effective with this protocol amendment, accrual to the Basket Cohort was suspended. Emerging literature allowed for the identification of specific tumor types that were more likely to respond to Sym015 treatment (e.g., NSCLC). With this change, a new Cohort of NSCLC MET-amplified patients had been added to Part 2 of the study design, for a total of three Cohorts. 2. With the suspension of the Basket Cohort, NSCLC MET-amplified patients entered to the Basket Cohort were counted toward the NSCLC MET-Amplified Cohort; NSCLC METEx14Del patients entered to the Basket Cohort were counted toward the NSCLC METEx14Del Cohort; patients with both were counted as MET-Amplified. 3. Updated clinical experience information had been added to the scientific background. 4. According to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for testing of HER2 amplification, MET amplification was defined as positive with a MET/CEP7 ratio of > 2.2 (occasionally 2.0). Symphogen had opted to change the cut-off to > 3.0 based on emerging data that suggest higher degrees of MET-amplification were associated with higher degree of response. 5. It was specified that concomitant therapy with bisphosphonates and denosumab were allowed during the dosing portion of the study. 6. It was clarified that after the screening assessments, targeted physical examination may have been performed as indicated. 7. The number of PK time points was reduced for patients entered to the NSCLC Cohorts. 8. The mandatory post-dosing tumor biopsy scheduled to be performed at the EOC2 or upon disease progression was made optional. 9. It was clarified that all analyses were related to and used only in connection with the data collected in the present study as well as future development of Sym015.