Dacomitinib for Treatment of Patients in India With Metastatic Non Small Cell Lung Cancer With EGFR Activating Mutations

SINGLE ARM STUDY TO EVALUATE THE SAFETY OF DACOMITINIB FOR THE FIRST-LINE TREATMENT OF PARTICIPANTS IN INDIA WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)-ACTIVATING MUTATIONS

This is a Phase 4, open label, single arm, multi-center, prospective clinical trial of dacomitinib that will be performed in India. This study will enroll a sufficient number of participants to ensure that 100 participants are treated with dacomitinib. The primary objective of this study is to assess the safety and tolerability of dacomitinib. The secondary objective is to evaluate antitumor activity of dacomitinib by objective response rate and duration of response.

This is a Phase 4, open label, single arm, multi-center, prospective clinical trial of dacomitinib that will be performed in India. This study will enroll a sufficient number of participants to ensure that 100 participants are treated with dacomitinib. The primary objective of this study is to assess the safety and tolerability of dacomitinib. The secondary objective is to evaluate antitumor activity of dacomitinib by objective response rate and duration of response. Drug administration: Dacomitinib will be supplied by Pfizer and administered in accordance with the India Local Product Document (LPD). The recommended dosage of dacomitinib is 45 mg taken orally once a day at approximately the same time each day, until disease progression, participant refusal/lost to follow-up, or unacceptable toxicity occurs.

STUDY PROCEDURES:

Screening: Participants will be screened within 28 days prior to first dosing of dacomitinib to confirm that they meet the eligibility criteria for the study.

Follow-up Visit: All participants will return to the study site up to 28 days after the last dose of study drug administration for assessment of potential AEs, recording of concomitant treatment use and to confirm appropriate contraception usage.

ASSESSMENTS Tumor Assessments: Tumor assessments will include all known or suspected disease sites. Computerized tomography (CT) or Magnetic resonance imaging (MRI) scans of Chest Abdomen and Pelvis and MRI of the brain will be performed at Screening and repeated every 12 weeks ±1 week until the end of treatment. For all tumor assessments, the method of assessment that was used at Screening will be used throughout the study. Tumor assessment will be repeated at the end of treatment if more than 6 weeks have passed since the last evaluation. Assessment of response will be made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Confirmation of response will be required ≥4 weeks after initial response is observed.

Safety Assessments: The following parameters will be assessed - Physical examination, vital signs, Eastern Cooperative Oncology Group Performance score (ECOG PS), safety lab data, 12 lead electrocardiogram (ECG). Unscheduled clinical laboratory measurements may be obtained at any time during the study to assess any perceived safety concerns.

Adverse event reporting: All observed or volunteered AEs regardless of treatment group or suspected causal relationship to the investigational product(s) will be reported as per regulatory requirements.

End of Study: The end of study is defined as 1 year after the last participant first visit (LPFV) date in the study. At the end of study, participants who are on treatment and benefiting from dacomitinib treatment will be switched to commercially available dacomitinib if considered appropriate by the investigator, as soon as feasible.

Inclusion Criteria:

1. Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC with EGFR activating mutations as detected by an appropriate test.
2. No prior treatment with systemic therapy and EGFR/Other Tyrosine Kinase Inhibitors (TKIs) for metastatic NSCLC.
3. Participants with asymptomatic Central Nervous System (CNS) metastases (including participants controlled with stable or decreasing steroid use within the last 2 weeks prior to study entry) will be eligible.
4. Age >=18 years.
5. ECOG PS of 0-2.
6. Adequate . hematologic, renal, liver function: ANC >= 1000/mm3; Platelets>=50000/mm3; Hb >=8 g/dL; est. Cr.Cl >=30 mL/min; Total serum bilirubin <1.5 × ULN; AST,ALT <=2.5 × ULN; (<=5.0 × ULN, if liver metastases).
7. Acute effects of any prior therapy resolved to baseline severity or to Common Terminology Criteria for Adverse Events (CTCAE) Grade <1 except for AEs that in the investigator's judgment do not constitute a safety risk for the participant.
8. Serum or urine pregnancy test (for females of childbearing potential) negative at Screening.

Exclusion Criteria:

1. Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.
2. Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation.
3. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Prior irradiation to >25% of the bone marrow.
4. Major surgery within 4 weeks prior to first dose of dacomitinib. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
5. Known prior or suspected severe hypersensitivity to dacomitinib or any component of its formulation.
6. History or known presence of interstitial fibrosis, interstitial lung disease, pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis.
7. Other severe acute or chronic medical or psychiatric condition, that may interfere with the interpretation of study results and, would make the participant inappropriate for entry into this study.
8. Evidence of active malignancy (other than current NSCLC) within the last 3 years prior to first dose of dacomitinib.
9. Breastfeeding female participants.
10. Pregnant female participants; male participants able to father children and female participants of childbearing potential who are unwilling or unable to use contraception method per protocol