Lung Cancer Non Small Cell Lung Cancer
Conditions
Interventions
None listed
Sponsors
QIAGEN
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent 2. >=18 years of age (or meets the country*s regulatory definition for legal adult age, whichever is greater) 3. Histologically or cytologically confirmed, locally advanced, non-resectable or metastatic NSCLC 4. Has received the following prior treatment and no more than 2 lines of prior cytotoxic chemotherapy for locally advanced or metastatic disease setting: a. Part A1 (Phase 1 Dose Escalation): Standard of care (SOC) that is available to the patient, unless contraindicated or intolerable to the patient b. Part A2: Progression on third-generation EGFR TKI (eg, osimertinib, lazertinib) and having received or not eligible for platinum-based chemotherapies or other targeted approved therapies in case of off-target alterations. c. Parts B, and C: Progression on third-generation EGFR TKI (eg, osimertinib, lazertinib) 5. Has the following EGFRmt status as determined by a CLIA certified (US), locally certified (outside of the US), or the study central laboratory based on tumor tissue or plasma cfDNA: a. Part A1 (Phase 1 Dose Escalation): Any EGFRmt b. Parts A2, B, and C: Any sensitizing EGFRmt and a confirmed C797S EGFRmt (Note: no T790M EGFRmt required) 6. Has tumor tissue available collected after progression on the most recent systemic EGFR TKI treatment in a quantity sufficient to allow for analysis of EGFRmt status by the Sponsor*s central laboratory (optional for Part A1 only). Please refer to the Laboratory Manual for details. 7. Has measurable disease per RECIST v1.1 (optional for patients in Part A1) 8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 9. Adequate organ function as defined by the following criteria: a. Absolute neutrophil count (ANC) >= 1.5 × 109/L b. Platelet count >= 100,000/mm3 (>= 100 × 109/L); last transfusion of blood products must be >=2 weeks prior to start of study treatment. c. Hemoglobin >= 9.0 g/dL d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =50 mL/min. For calculated CrCl, use the Cockcroft-Gault formula g. Potassium blood levels >=3.0 mmol/L 10. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of study treatment. Female patients are not considered to be of child-bearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 11. Both males and females of reproductive potential must agree to use highly effective birth control throughout the study and at least for: * 6 months after the last dose of study treatment for females * 3 months after the last dose of study treatment for males or longer, based on local requirements In addition to the above, patients in France must meet the following criterion: 12. Affiliated with a social security system or be a beneficiary of an <br
Exclusion criteria
Exclusion criteria: 1.Currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study 2. Has received prior treatment with any of the following within the specific time frame prior to the first dose of study treatment: a. Major surgery/surgical therapy for any cause within 4 weeks; the patient must have recovered adequately from the toxicity and/or complications of the intervention prior to starting study treatment b. Chemotherapy, biologic therapy, targeted therapy, immunotherapy, or investigational agents within 5 half-lives or within 4 weeks (whichever is shorter) prior to the first dose of study treatment. Patient must have recovered from toxicities of the prior therapy based on the Investigator*s judgement prior to starting study treatment c. No prior treatment with: (i) Part A1 (Phase 1 Dose Escalation): Systemic immunotherapy (eg, PD- 1/PD-L1 antibody) (ii) Parts A2, B, and C: Any EGFR C797S mutation-targeting agent (eg, BLU-945) d. Radiotherapy prior to the start of study treatment within: (i). 2 weeks for radiation therapy of non-thoracic regions (7 days for palliative radiation of single lesions) (ii). 3 months for radiation therapy including thoracic region. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. 3. Have any unresolved clinically relevant toxicity of Grade >= 2 from previous anti-cancer treatment, except for alopecia, skin pigmentation, and Grade 2, prior platinum-therapy related neuropathy. Patients with chronic, but stable Grade 2 toxicities may be allowed to enroll if the Investigator and Sponsor agree. 4. Any strong and moderate inhibitors/inducers of cytochrome P450 (CYP) 3A two weeks prior to start of therapy. If a patient is receiving strong inhibitors/inducers of CYP3A , these medications and substances must be discontinued >=2 weeks prior to the first dose of study treatment. 5. Has the following CNS metastases disease status: a. Part A1 (Phase 1 Dose Escalation): Known untreated central nervous system (CNS) metastases, or history of uncontrolled seizures, or leptomeningeal disease. Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period, and they are on a stable or decreasing dose of corticosteroids for at least 2 weeks prior to the first dose of study treatment. b. Part A2, B, and C: Spinal cord compression, symptomatic and unstable CNS metastases, requiring steroids over the last 4 weeks prior to enrollment (asymptomatic and symptomatic brain metastases stable for at least 4 weeks and off steroids are allowed). Patients with leptomeningeal disease are allowed if it is determined that immediate CNS treatment is unlikely to be required. 6. Impaired cardiac function or clinically significant cardiac disease, including any of the following: a. Baseline QT interval > 470 msec corrected for heart rate using Fridericia*s formula (QTcF, verified on repeat measure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the Phase 1 Dose Escalation part of this study is to identify the RP2D based on safety and preliminary antitumor activity observed as standard for Phase 1 first in human studies. The primary endpoint of the Phase 1 Dose Expansion and the Phase 2 part is Overall response rate (ORR) assessed by Independent Central Review (ICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. ORR is a clinically meaningful and accepted endpoint by regulatory agencies for studies in later-line EGFRmt NSCLC patients. ORR will be assessed by ICR to avoid any potential Investigator bias and to increase the validity of the ORR results observed. | — |
Secondary
| Measure | Time frame |
|---|---|
| As a key secondary objective, this study will include Duration of response (DoR) as assessed by ICR to evaluate the durability of responses. Durability of responses are considered a key factor to determine whether an observed ORR is clinically meaningful. | — |
Countries
Netherlands
Outcome results
None listed