Phase 2 Rare Disease Trial, Recruiting

Written by an AI model from ClinicalTrials.gov eligibility criteria and checked on a sample basis. Please confirm against the original criteria.

Who might be able to join this trial:

• People aged 18 or older (or the legal adult age in their country, whichever is higher) who have given written consent to participate.
• People who have been diagnosed with advanced or spreading non-small cell lung cancer (NSCLC) that has been confirmed by a laboratory test.
• Group A: People whose cancer has a specific gene change called EGFR exon 20 insertion (ex20ins), confirmed by a certified lab, and whose cancer has continued to grow during or after treatment with a medicine that specifically targets this gene change (such as amivantamab, sunvozertinib, or BLU451), either alone or combined with standard chemotherapy — including people who had to stop that treatment due to severe side effects.
• Group A (brain spread): People in Group A who have cancer that has spread to the brain may still be eligible if their condition is neurologically stable, they have already received brain-directed treatment with no signs of cancer growth for at least 4 weeks, and they have been on a stable or reducing dose of steroid or anti-seizure medicines for at least 2 weeks before starting the trial.
• Group B: People whose cancer has the EGFR ex20ins gene change, confirmed by a certified lab, who have not yet received treatment for their advanced or spreading cancer, and who are either not suitable for standard first-line platinum-based chemotherapy (as judged by the treating doctor) or who have declined that chemotherapy after discussion with their doctor.
• Group B (prior early-stage treatment): People in Group B who previously received treatment before or after surgery for early-stage disease may be eligible if that treatment was completed more than 6 months before starting the trial.
• Group B (brain spread): People in Group B who have cancer that has spread to the brain may still be eligible if the same brain stability conditions described for Group A are met.
• Group C: People whose cancer has the EGFR ex20ins gene change or certain other uncommon EGFR gene changes (non-ex20ins), confirmed by a certified lab, and who have cancer that has spread to the brain in a way that can be measured or confirmed, including newly diagnosed or growing brain tumours not yet treated with brain-directed therapy, or a specific type of spread into the fluid around the brain and spine (called leptomeningeal disease, or LMD), confirmed by a fluid or imaging test.
• Group D: People whose cancer has certain other uncommon EGFR gene changes (not ex20ins, and not the specific change called C797S), confirmed by a certified lab, who have not yet received systemic treatment for their advanced or spreading cancer, and whose early-stage treatment (if any) was completed more than 6 months before starting the trial and did not include any EGFR-targeted medicines known as TKIs.
• Group D (brain spread): People in Group D who have cancer that has spread to the brain may still be eligible if the same brain stability conditions described for Group A are met.
• People who have measurable cancer that can be tracked using standard imaging criteria (RECIST 1.1).
• People who have tumour tissue available from a previous biopsy that can be sent to the lab for testing.
• People whose general health and ability to carry out daily activities is rated as fully active or restricted in strenuous activity only (ECOG performance status 0 or 1).
• People whose blood, kidney, and liver function results are within acceptable ranges as defined by the trial.
• Women who could become pregnant must have a negative blood pregnancy test before starting treatment.
• All people who could father or become pregnant must agree to use effective contraception during the trial and for 1 month after the last dose.
• Drug interaction sub-study: People with confirmed advanced NSCLC with a range of EGFR gene changes (including ex20ins, other uncommon types, or common types such as exon 19 deletion or L858R), who have already received standard treatment for advanced disease, or for whom standard treatment is not appropriate, is not tolerated, or has been declined after being fully informed.
• Dose optimisation sub-study: People with confirmed advanced NSCLC with the EGFR ex20ins gene change whose cancer has continued to grow during or after standard platinum-based chemotherapy, including those who stopped due to side effects (prior treatment with amivantamab is also permitted in this group).
• Dose optimisation sub-study (brain spread): People in this sub-study with cancer spread to the brain may be eligible if their brain tumours can be measured according to specific imaging criteria, and they have either already received definitive brain treatment and have been stable and off steroids for at least 2 weeks, or have small, symptom-free brain tumours that the treating doctor considers do not immediately require treatment.

Who may not be able to join:

• People who are currently taking part in another clinical trial or medical research study that the trial team considers incompatible with this trial.
• People who have ever previously received the study drug zipalertinib (TAS6417/CLN081).
• People who have received brain radiation therapy (other than a specific type called gamma knife) within the past 12 weeks, chest radiation within the past 28 days, or other palliative radiation within the past 14 days before the first dose.
• People who have received cancer immunotherapy within the past 28 days before the first dose.
• People who have had major surgery (not including insertion of a vascular access line) within the past 28 days before the first dose.
• People who have previously received any EGFR exon 20 insertion-targeted TKI medicine (note: this applies to certain groups — confirm with trial site which groups this affects).
• People who have cancer that has spread into the fluid surrounding the brain and spine (leptomeningeal disease), except in Group C where this may be an inclusion criterion (confirm with trial site).
• People who still have unresolved significant side effects (grade 2 or higher) from previous cancer treatment, except for hair loss or skin colour changes at grade 2, or other stable long-term grade 2 side effects that the trial site and sponsor agree are acceptable.
• People with a past history of a lung condition called interstitial lung disease, or lung inflammation caused by a previous treatment, or any currently active interstitial lung disease.
• People with significant heart problems, including severe heart failure (class III or IV), serious irregular heart rhythms requiring treatment, or an abnormal heart electrical reading (QTc above 470 milliseconds).
• People who are unable to swallow tablets, or who have a condition that could significantly affect how the body absorbs the study drug (such as inflammatory bowel disease, malabsorption conditions, or previous removal of part of the stomach or bowel).
• People who have been diagnosed with another cancer within the past 2 years, unless it was a treated skin cancer (basal or squamous cell), breast or cervical cancer in situ, a cancer fully treated more than 2 years ago with no signs of return, or a concurrent cancer that is stable and not currently requiring treatment.
• People with known hepatitis B, hepatitis C, or HIV that is not being controlled with treatment.
• People who have had a COVID-19 infection within the past 4 weeks before joining, or who still have significant ongoing lung symptoms from a previous COVID-19 infection.
• People with active bleeding disorders.
• People with a known allergy to zipalertinib or medicines with a similar structure or class.
• People who are pregnant, breastfeeding, or planning to become pregnant.
• People who, in the treating doctor's opinion, are unable or unwilling to follow the trial procedures.

Important: Always verify eligibility with the trial site directly before applying.