An Open Label, First-in-human Study of BAY 2927088 in Participants With Advanced Non-small Cell Lung Cancer (NSCLC) Harboring an EGFR and/or HER2 Mutation
Overview
- Phase
- Phase 1
- Intervention
- BAY2927088_formulation A
- Conditions
- Not specified
- Sponsor
- Bayer
- Enrollment
- 370
- Locations
- 152
- Primary Endpoint
- Number of participants with treatment-emergent serious adverse events (TESAEs)
- Status
- Active, not recruiting
- Last Updated
- 18 days ago
Overview
Brief Summary
Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other parts of the body.
Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are proteins that help cells to grow and divide. A damage (also called mutation) to the building plans (genes) for these proteins in cancer cells leads to a production of abnormal EGFR and/or HER2. These abnormal proteins drive the growth and the spread of the cancer. Several EGFR and/or HER2 mutations exist in the cancer cells. The study treatment, BAY2927088, is expected to block the mutated EGFR and HER2 proteins which may stop the spread of NSCLC.
The main purpose of this study is to learn:
Escalation, Backfill, and Expansion Part:
- How safe is BAY2927088 for the participants?
- What is the highest dose of BAY2927088 that can be tolerated (maximum tolerated dose) by or given to (maximum administered dose) the participants?
- How does BAY2927088 move into, through, and out of the bodies of the participants?
For this, the researchers will measure the followings:
- The number of participants with medical problems, also called adverse events and serious adverse events, and their severity
- The number of participants who discontinue study treatment due to an adverse event.
- The highest dose of BAY2927088 that the participants can take without having adverse events (maximum tolerated dose (MTD)) or the maximum dose that is tested and found to be safe for the participants in case MTD cannot be found out (maximum administered dose (MAD)) of BAY2927088
- Number of participants experiencing adverse events that prevent an increase in the dose of BAY2927088 (dose-limiting toxicities (DLTs)) at each dose level
- The (average) total level of BAY2927088 in the blood (also called AUC) after receiving single or multiple doses of BAY2927088
- The (average) highest level of BAY2927088 in the blood (also called Cmax) after receiving a single or multiple doses of BAY2927088 Extension Part
- How well does BAY2927088 work in participants?
For this, the researchers will measure the following:
• Percentage of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)). This will be assessed by doctors other than the study doctor.
This study has 4 parts:
- The escalation part aims to find the maximum daily amount (dose) of BAY2927088 that participants can receive.
- The backfill part aims to test the doses of BAY2927088 that are considered safe in the escalation part by giving it to more participants. This will help find optimal doses of BAY2927088 that work well and are safe to be tested in the next part.
- The expansion part aims to determine the dose of BAY2927088 to be tested in further studies.
- The extension part aims to determine whether the selected dose of BAY2927088 from the expansion part works well.
The participants in this study will take the study treatment BAY2927088 in 3-week periods called "cycles". They will in general take BAY2927088 once or twice daily as a liquid/tablet by mouth until their cancer gets worse, they have medical problems, they leave the study, or the study is terminated. Participants will have no more than 5 visits per cycle.
During the study, the study team will:
- take blood and urine samples,
- check the status of the cancer by doing computed tomography (CT) or magnetic resonance imaging (MRI) scans,
- check the participants' overall health and heart health,
- ask the participants questions about how they are feeling and what adverse events they are having.
An adverse event is considered "serious" when it leads to death, puts the participant's life at risk, requires hospitalization, causes disability, causes a baby being born with medical problems, or is medically important.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented histologically or cytologically confirmed locally advanced NSCLC, not suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small cell or mixed histologies are excluded).
- •Documented disease progression after treatment with at least one prior systemic therapy for advanced disease. Participants who do not have standard of care access due to any reason, are intolerant to, or are not eligible for standard treatments, may also be eligible.
- •Note: Except for participants eligible for one of the groups (Expansion or Extension) who should have received no prior systemic treatment for locally advanced or metastatic disease.
- •Adequate archival tumor tissue (ideally taken after last targeted treatment and not older than 6 months) has to be available, either from primary or metastatic sites. If archival material is not available, a fresh tumor biopsy should be performed if feasible and if the procedure poses no significant risk for the participant.
- •Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy during the screening period (if a biopsy is taken during screening) that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied lesion should not be used as a target lesion for RECIST 1.1 tumor assessments (or, for participants in Expansion Group G, for RANO-BM tumor assessments). Previously irradiated lesions must have shown progression to be considered measurable.
- •Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (United States \[US\] sites) or an equally accredited (outside of the US) local laboratory
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Minimum life expectancy of 12 weeks.
- •Adequate bone marrow function as assessed by the following laboratory tests to be conducted within 7 days before the first dose of study treatment:
- •Hemoglobin ≥ 9.0 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.
Exclusion Criteria
- •Treatment with an EGFR tyrosine kinase inhibitor (TKI) ≤ 8 days or 5x the terminal phase, elimination half-lives, whichever is shorter, prior to the first dose of study drug.
- •Treatment with a systemic anti-cancer treatment (excluding EGFR TKIs as described above) ≤ 14 days prior to the first dose of study drug.
- •Radiation therapy, stereotactic radiosurgery (SRS) and palliative radiation ≤ 14 days prior to the first dose of study drug.
- •Treatment with immunotherapy ≤ 28 days prior to the first dose of study drug.
- •Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
- •Any history of primary brain or leptomeningeal disease (symptomatic or asymptomatic), presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local treatment (such as radiotherapy or surgery).
- •History of spinal cord compression or brain metastases with the following exceptions:
- •Participants with treated brain metastases that are asymptomatic at screening and who are off or receiving low-dose corticosteroids (≤10 mg prednisone or equivalent) for at least 7 days prior to first dose of BAY 2927088 are eligible to enroll in Dose Escalation and Backfill.
- •Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion/Extension (with the exception of Group G) if all of the following criteria are met:
- •there is no evidence of progression (new or enlarging brain metastases) for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
Arms & Interventions
Dose escalation
Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD.
Intervention: BAY2927088_formulation A
Dose escalation
Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD.
Intervention: BAY2927088_formulation B_1
Dose escalation
Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD.
Intervention: BAY2927088_formulation B_2
Backfill
Dose Escalation and Backfill run concurrently
Intervention: BAY2927088_formulation A
Backfill
Dose Escalation and Backfill run concurrently
Intervention: BAY2927088_formulation B_1
Backfill
Dose Escalation and Backfill run concurrently
Intervention: BAY2927088_formulation B_2
Dose expansion
Eight independent groups (group A, B1, B2, C, D, E, F, G) are planned. Dose Expansion may start at a dose level that has been evaluated in Escalation/Backfill in at least 9 participants and considered safe or at any other dose levels that are below the highest dose level that is considered safe.
Intervention: BAY2927088_formulation B_1
Dose expansion
Eight independent groups (group A, B1, B2, C, D, E, F, G) are planned. Dose Expansion may start at a dose level that has been evaluated in Escalation/Backfill in at least 9 participants and considered safe or at any other dose levels that are below the highest dose level that is considered safe.
Intervention: BAY2927088_formulation B_2
Extension part
Initiation of the Extension part will depend on the benefit-risk profile observed during Dose Expansion. Additionally, enrollment may be prematurely terminated based on emerging data at the discretion of the Sponsor.
Intervention: BAY2927088_formulation B_1
Extension part
Initiation of the Extension part will depend on the benefit-risk profile observed during Dose Expansion. Additionally, enrollment may be prematurely terminated based on emerging data at the discretion of the Sponsor.
Intervention: BAY2927088_formulation B_2
Outcomes
Primary Outcomes
Number of participants with treatment-emergent serious adverse events (TESAEs)
Time Frame: Up to 30 days after the last administration of study treatment
Severity of TEAEs
Time Frame: Up to 30 days after the last administration of study treatment
Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2927088 within the DLT observation period in Dose Escalation (including participants from Backfill qualifying for the MTD population)
Time Frame: At the end of Cycle 1 of a 21-day cycle
Cmax of BAY2927088
Time Frame: Cycle 1, Day 1 (Cycle duration is 21 days)
Cmax: Maximum/peak concentration
Cmax,md of BAY2927088
Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days)
Cmax,md: Cmax after multiple dose administrations
Number of participants with treatment-emergent adverse events (TEAEs)
Time Frame: Up to 30 days after the last administration of study treatment
Severity of TESAEs
Time Frame: Up to 30 days after the last administration of study treatment
AUC(0-24) of BAY2927088 for QD
Time Frame: Cycle 1, Day 1 (Cycle duration is 21 days)
AUC: Area under the concentration vs. time curve. AUC(0-24): AUC from time 0 to 24 hours post dose. QD: Quaque die (once daily)
Number of participants who discontinue study treatment due to an AE
Time Frame: About 4 years (Up to the end of study treatment)
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR) in extension part
Time Frame: From the start of the study treatment up to 12 months
Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY2927088 in the DLT observation period in Dose Escalation (including participants from Backfill)
Time Frame: At the end of Cycle 1 of a 21-day cycle
In Dose Escalation (including participants from Backfill)
AUC(0-12) of BAY2927088 for BID
Time Frame: Cycle 1, Day 1 (Cycle duration is 21 days)
If applicable. AUC(0-12): AUC from time 0 to 12 hours post dose. BID: Bis in die, 2 times daily.
AUC(0-24)md of BAY2927088 for QD
Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days)
AUC(0-24)md: AUC(0-24) after multiple dose administrations
AUC(0-12)md of BAY2927088 for BID
Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days)
If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations
Secondary Outcomes
- Recommended phase 2 dose (RP2D) of BAY2927088(About 1.5 years)
- Overall response rate (ORR) as per RECIST v1.1 by investigator assessment(About 4 years)
- ORR per RECIST v1.1 by Investigator assessment in extension part(From the start of the study treatment up to 12 months)
- Overall survival (OS) in extension part(From the start of the study treatment up to 12 months)
- Disease control rate (DCR) per RECIST v1.1 by Investigator assessment and BICR in extension part(From the start of the study treatment up to 12 months)
- Duration of response (DOR) per RECIST 1.1 by Investigator assessment and BICR in extension part(From the start of the study treatment up to 12 months)
- Progression-free survival (PFS) per RECIST 1.1 by Investigator assessment and BICR in extension part(From the start of the study treatment up to 12 months)
- Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity in extension part(Up to 30 days after the last administration of study treatment)