Phase-2 Dacomitinib Study on Patients With EGFR-Driven Advanced Solid Tumours With Low EGFR-AS1 IncRNA Expr or Other Novel Emerging Biomarkers

Provision of a voluntarily given, personally signed and dated, written informed consent document. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness;Age ≥ 21 years, male or female; Documentation of the presence of low EGFR-AS1 lncRNA expression as determined using the specifically designed companion diagnostic biomarker suite provided by the Sponsor (cohorts 1 to 3) or the presence of a novel emerging biomarker of EGFR family pathway addiction as determined by the Sponsor (cohort 4);

Study cohorts:

Cohort 1: advanced or metastatic EGFR wildtype squamous NSCLC, after progression on or after, or intolerance to, one or more lines of standard of care (SOC) therapy, per local SOC guidelines. In subjects without an activating oncogenic driver mutation, after progression on or after, or intolerance to, platinum-containing combination chemotherapy. In subjects harbouring an activating oncogenic driver mutation, after progression on one or more SOC mutation-targeting TKI, per local SOC guidelines, or for whom no SOC mutation-targeting TKI is available. TKI therapy need not be the most recent prior therapy. Subjects harbouring an activating EGFR mutation are not eligible;Cohort 2: advanced or metastatic head and neck squamous cell carcinoma, after progression on or after, or intolerance to, platinum-containing combination chemotherapy. This need not be the most recent or prior regimen; Cohort 3: all advanced or metastatic solid tumours (excluding squamous NSCLC and HNSCC), after progression on or intolerance to at least one line of SOC therapy per local guidelines; Cohort 4: all advanced or metastatic solid tumours, after progression on or intolerance to at least one line of SOC therapy per local guidelines; Have an ECOG PS of ≤2; Life expectancy of at least 3 months; Site of disease amenable to biopsy and be a candidate for tumour biopsy according to the treating institution's own guidelines and requirements for such procedure. Subjects must be willing to undergo a tumour biopsy at screening, and on treatment on this study;

Radiologically measurable disease by RECIST v1.1 criteria:

At least one target lesion that has not previously been radiated and is measurable according to RECIST v1.1;Acceptable radiologic procedures for disease assessment include contrast enhanced conventional or spiral computed tomography (CT), or contrast enhanced magnetic resonance imaging (MRI);Non contrast CT scan is acceptable only for subjects who are both allergic to intravenous contrast and unable to cooperate with MRI, or MRI is not available. The following are not allowed as sole documentation of target lesions: CT component of a positron emission tomography (PET)/CT, ultrasound alone, nuclear scans (including bone or PET scans), chest X-ray or bone radiographs, and tumour markers;

Adequate organ function, including:

Estimated creatinine clearance ≥30 mL/min (as determined by Cockcroft-Gault formula or the study site's standard formula);Absolute neutrophil count (ANC) ≥1500 cells/mm3; Platelets ≥100,000 cells/mm3; Hemoglobin ≥10.0 g/dL; Bilirubin ≤1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST; also known as SGOT) and Alanine aminotransferase (ALT; also known as SGPT) ≤2.5 x ULN (≤5.0 x ULN if hepatic metastases).

Female subjects must be postmenopausal (defined as 12 months of amenorrhea following last menses), or they or their partners must be surgically sterile, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the investigator using following criteria:

Acceptable contraception for women include implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence, or a partner who has been surgically sterile (e.g. by vasectomy) for at least 6 months. Acceptable contraception for a male includes surgical sterility (e.g. by vasectomy) for at least 6 months, sexual abstinence, or condoms plus spermicide.All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) before starting study treatment; Male subjects or their female partners must be surgically sterile or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the investigator. Or female partners must be postmenopausal (defined as 12 months of amenorrhea following last menses); Willing and able to comply with study scheduled visits, treatment plans, laboratory tests, and other study procedures.