New drug combo aims to tackle tough lung cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Participants must be able to provide documented informed consent. 2. Aged ≥ 18 years. 3. Histologically or cytologically confirmed diagnosis of non-squamous NSCLC, locally advanced or metastatic, not suitable for curative therapy. 4. Documentation of EGFR mutation from a local certified laboratory. Part A: EGFR mutations (excluding participants only harboring EGFR exon20ins). Part B: EGFR sensitizing mutations (Exon19del and/or L858R) with or without T790M/C797S resistance mutations. 5. Provide adequate baseline tumor and plasma samples. For part A: tumor samples collected after disease progression on the last EGFR TKI treatment. For part B: tumor samples of B1 and B2 cohorts should be collected after disease progression on the last EGFR TKI treatment. Tumor samples of B3 cohort should be collected before the study treatment. 6. Previous anti-tumor therapy requirement. For part A, B1, and B2 cohorts of part B: participants should have failed (progressed on or are intolerant to) one line of third-generation EGFR TKI regimen (such as Osimertinib), with (cohort B2) or without (cohort B1) prior platinum-based chemotherapy treatment. Participants could receive no more than 2 lines of EGFR TKI treatment and no more than 3 lines of systemic therapy. Participants in B3 cohort: should not receive prior systemic anti-tumor therapy. 7. ECOG 0 or 1 with predicted life expectancy ≥ 12 weeks. 8. Brain metastases must be stable at study entry. 9. Measurable disease per RECIST 1.1. 10. Adequate hematopoietic and other organ system functions. Exclusion Criteria: 1. NSCLC with mixed small-cell lung cancer (SCLC) or NSCLC with histologic SCLC transformation. 2. For part A: participants only harboring EGFR exon20ins（harboring other EGFR mutations could be enrolled）. 3. Prior treatment with any of the following: 1) Previously received two or more than two lines of third-generation EGFR TKI treatment. 2) Previously received systemic anti-cancer therapy for advanced disease (only for B3 cohort). 3) Immunotherapy or other antibody therapy within 4 weeks prior to the first administration; 4) Any cytotoxic chemotherapy, investigational drugs or other anticancer drugs from a previous treatment regimen or clinical study within 14 days prior to the first administration; 5) Radiotherapy with a limited field of radiation for palliation within 7 days of the first administration, radiation to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first administration; 6) Currently receiving or unable to stop drug or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP)3A4. A washout period of at least 2 weeks for strong inhibitors and 3 weeks for strong inducers is required prior to the first study drug administration; 7) Currently receiving or unable to stop drugs known to be CYP3A4 sensitive substrate with a narrow therapeutic index. A washout period of at least 2 weeks is required prior to the first study drug administration; 8) Currently receiving or unable to stop drugs known to be proton-pump inhibitors. A washout period of at least 1 week is required prior to the first study drug administration; 9) Major surgery within 4 weeks of the first administration of study drug administration or anticipated during the study period. 4. Any unresolved toxicities from prior anti-cancer therapy greater than CTCAE Grade 1. 5. Spinal cord compression or leptomeningeal metastasis. 6. Participants with any other malignancy within 2 years of the first administration of the study drug. 7. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses as judged by the investigator. 8. Participants with active infection, including but not limited to HBV, HCV and HIV. 9. Resting QTcF \> 470 msec; Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG; Any factors that increase the risk of QTc prolongation. 10. Past medical history of ILD or active ILD. 11. Diseases that would preclude adequate absorption of study drug. 12. Received a live vaccine within 2 weeks before the first administration of study drug. 13. Women who are pregnant or breastfeeding. 14. Hypersensitivity to active or inactive excipients of DZD6008, sunvozertinib or osimertinib (only for B3 cohort).