A phase 1/2 open-label multicenter study will be performed with an initial dose escalation part to determine the MTD and/or the RP2D of MCLA-129 as monotherapy as well as in combination with chemotherapy in patients with NSCLC harboring an activating EGFR mutation or activating c-MET mutation/amplification.
At present expansion phase II for inclusion for patients harboring an EGFR mutation and progressed on 1L osimertinib (cohort F) or progressed on 1L osimertinib and 2L platinum treatment (cohort G).

Patient will receive MCLA-129+ carboplatin/paclitaxel (cohort F) or MCLA-129+ docetaxel (cohort G).

To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of MCLA-129 as monotherapy as well as in combination with chemotherapy in patients with NSCLC, with disease progression after prior therapy for advanced/metastatic disease.

To evaluate clinical activity, as assessed by ORR, of MCLA-129 monotherapy or in combination with an EGFR TKI or chemotherapy in populations of advanced/metastatic solid tumors.

• Signed informed consent before initiation of any study procedures.
• Age ≥18 years at signature of informed consent.
• Availability of tissue sample FFPE embedded after progression at the latest therapy
  (preferred in escalation, mandatory in expansion). Sequential biopsies are mandatory (before start study and after 8 days).
• Measurable disease as defined by RECIST version 1.1 by radiologic methods (patients with non-measurable but evaluable disease can be included in the dose escalation part).
• Progression on 1L osimertinib (cohort F) or progression on 1L osimertinib and 2L platinum-pemetrexed (cohort G).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥12 weeks, as per Investigator judgment.
• Adequate organ function, as per Investigator judgment.

• Central nervous system metastases that are untreated or symptomatic, require radiation or surgery, or require continued steroid therapy.
• Known leptomeningeal involvement.
• Systemic anticancer therapy or immunotherapy within 4 weeks or 5 half-lives
  (whichever is shorter) of the first dose of study treatment.
• Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.
• Persistent Grade >1 clinically significant toxicities, in the Investigator judgment, related to prior antineoplastic therapies (except for alopecia); stable sensory neuropathy Grade ≤2 NCI-CTCAE v5.0 and hypothyroidism Grade ≤2 which is stable on hormone replacement are allowed.
• History of hypersensitivity reaction or any toxicity attributed to human proteins or any of the excipients that warranted permanent cessation of these agents. History of hypersensitivity reaction or any toxicity attributed to chemotherapy and components.
• History of clinically significant cardiovascular disease.
• Past medical history of ILD or pneumonitis, or any evidence of clinically active ILD or pneumonitis.
• Previous or concurrent malignancy, excluding non-basal cell carcinomas of skin or carcinoma in situ of the uterine cervix, unless the tumor was treated with curative or palliative intent and in the opinion of the Investigator, with Sponsor agreement, the previous or concurrent malignancy condition does not affect the assessment of safety and efficacy of the study treatment (dose expansion phase only).