Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication HYRNUO is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 ( ERBB2 ) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1) ] , and who have received a prior systemic therapy. FDA label
Also known as BAY2927088, [14C]-BAY2927088 oral solution, Sevabertinib (BAY 2927088), BAY2927088_formulation B_1
Sevabertinib · 8 trials · 10 indications
RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR)
ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) per RECIST 1.1 by BICR. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \<10 mm. PR is defined as a ≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR)
To assess the influence of hepatic impairment on sevabertinib exposure. AUC from time zero to the last data point larger than the lower limit of quantification (LLOQ) (AUC(0-tlast) and the unbound AUC(0-tlast) will be used as the main parameters if AUC cannot be reliably determined in all participants.
To assess the influence of hepatic impairment on sevabertinib exposure. AUC from time zero to the last data point larger than the lower limit of quantification (LLOQ) (AUC(0-tlast) and the unbound AUC(0-tlast) will be used as the main parameters if AUC cannot be reliably determined in all participants.
To assess the influence of hepatic impairment on sevabertinib exposure.
To assess the influence of hepatic impairment on sevabertinib exposure.
Cmax: Maximum observed drug concentration
AUC: Area under the concentration vs time curve from zero to infinity
Cmax: Maximum observed drug concentration
AUC: Area under the concentration vs time curve
In Dose Escalation (including participants from Backfill)
Cmax: Maximum/peak concentration
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)
If applicable. AUC(0-12): AUC from time 0 to 12 hours post dose. BID: Bis in die, 2 times daily.
Cmax,md: Cmax after multiple dose administrations
AUC(0-24)md: AUC(0-24) after multiple dose administrations
If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations
| Arm | Type | Description |
|---|---|---|
| Sevabertinib | EXPERIMENTAL | Participants will receive sevarbetinib 20 mg BID until disease progression per RECIST v1.1, unacceptable toxicity, or until any other withdrawal criteria. |
| Standard of care (SoC) | ACTIVE_COMPARATOR | Participants will receive SoC (pembrolizumab in combination with platinum-based chemotherapy, in 21-day cycles per the approved labels) until disease progression per RECIST v1.1, unacceptable toxicity, or until any other withdrawal criteria. Participants in the SoC arm will have the opportunity to crossover to receive sevabertinib when they experience disease progression. |
| BAY2927088 | EXPERIMENTAL | Adult participants with metastatic or unresectable solid tumors with HER-2 activating mutations including: colorectal, biliary tract, bladder, cervical, endometrial, breast, and other solid tumor types. Participants will receive BAY2927088 20 mg BID until disease progression per RECICST 1.1, unacceptable toxicity, or until any other withdrawal criteria. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BID: twice a day |
| Arm A: Moderate Hepatic Impairment | EXPERIMENTAL | Approximately 10 participants with moderate impaired hepatic function (Child-Pugh B) to achieve approximately 8 evaluable participants |
| Arm B: Normal Hepatic Function | EXPERIMENTAL | Approximately 10 matched control participants for Arm A with normal hepatic function |
| Healthy participants from United States | EXPERIMENTAL | The healthy volunteers will be confined to the clinic throughout the intervention period of the study. The study includes visits during screening, intervention, and follow-up. |
| BAY2927088 + Itraconazole (ITZ) | EXPERIMENTAL | Participant will receive single dose BAY2927088 on Days 1 and 8, will receive itraconazole daily from Day 5 to Day 11. |
| BAY2927088 + Carbamazepine (CBZ) | EXPERIMENTAL | Participant will receive BAY2927088 single dose on Days 1 and 14, will receive carbamazepine daily from Day 3 to Day 15. |
| Intervention A - Intervention B - Intervention C | EXPERIMENTAL | Intervention A: BAY2927088 is administered under fasted status. Intervention B: BAY2927088 is administered under fed status (light low-fat meal). Intervention C: BAY2927088 is administered under fed status (high fat, high calorie meal). Each participant will subsequently undergo a fourth intervention period that includes dosing with BAY2927088 and esomeprazole. |
| Intervention B - Intervention C- Intervention A | EXPERIMENTAL | Intervention A: BAY2927088 is administered under fasted status. Intervention B: BAY2927088 is administered under fed status (light low-fat meal). Intervention C: BAY2927088 is administered under fed status (high fat, high calorie meal). Each participant will subsequently undergo a fourth intervention period that includes dosing with BAY2927088 and esomeprazole. |
| Intervention C - Intervention A - Intervention B | EXPERIMENTAL | Intervention A: BAY2927088 is administered under fasted status. Intervention B: BAY2927088 is administered under fed status (light low-fat meal). Intervention C: BAY2927088 is administered under fed status (high fat, high calorie meal). Each participant will subsequently undergo a fourth intervention period that includes dosing with BAY2927088 and esomeprazole. |
| Healthy volunteers | EXPERIMENTAL | The healthy volunteers will be confined to the clinic throughout the Intervention Period of the study. The study includes visits during Screening, Intervention, and Follow-up. |
| Dose escalation | EXPERIMENTAL | Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD. |
| Backfill | EXPERIMENTAL | Dose Escalation and Backfill run concurrently |
| Dose expansion | EXPERIMENTAL | Eight independent groups (group A, B1, B2, C, D, E, F, G, H, I, J) 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. |
| Extension part | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| Sevabertinib | DRUG | Tablet, oral |
| Pembrolizumab | DRUG | Intravenous (IV) infusion |
| Cisplatin | DRUG | IV infusion |
| Carboplatin | DRUG | IV infusion |
| Pemetrexed | DRUG | IV infusion |
| BAY2927088 | DRUG | tablet, oral |
| Midazolam | DRUG | Oral administration |
| Itraconazole | DRUG | Capsule, 100 mg, oral. |
| Carbamazepine | DRUG | Tablet, 100 mg, 200mg and 300mg, oral. |
| Esomeprazole | DRUG | Oral administration |
| Food | OTHER | light low-fat meal or high fat, high calorie meal |
| Dabigatran etexilate | DRUG | Oral administration. |
| Rosuvastatin | DRUG | Oral administration. |
| BAY2927088_formulation A | DRUG | Oral administration |
| BAY2927088_formulation B_1 | DRUG | Oral administration |
| BAY2927088_formulation B_2 | DRUG | Oral administration |
| BAY2927088_formulation B_3 | DRUG | Oral administration |
Inclusion Criteria: * Participant must be ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signing the informed consent. * Documented histologically or cytologically confirmed locally advanced non-squamous NSCLC, not suitable for defi...
Sevabertinib is an investigational oral small molecule being studied for advanced non-small cell lung cancer with HER2 mutations and for advanced solid tumors carrying HER2 mutations. It is also being evaluated in pharmacokinetic studies involving healthy volunteers and in participants with moderate liver impairment. It is not yet approved for any use.
Sevabertinib targets HER2, the human epidermal growth factor receptor 2. It belongs to the kinase inhibitor class, often identified by the -tinib suffix. By acting on HER2, the drug is designed to address tumors that carry HER2 mutations, which is why the clinical program selects participants by HER2 biomarker status.
Sevabertinib is developed by Bayer AG, which trades under the ticker BAYRY. Bayer sponsors the clinical program, and the compound also appears in study documents under the code BAY2927088.
Sevabertinib is in Phase 1 development overall, with additional studies running at later stages. A Phase 3 trial in advanced non-small cell lung cancer with HER2 mutations is recruiting, and a Phase 2 trial in advanced solid tumors with HER2 mutations is also recruiting. Sevabertinib is investigational and not FDA approved.
Sevabertinib has been studied across five trials. The Phase 3 NSCLC study is NCT06452277, and the Phase 2 solid tumor study is NCT06760819, both recruiting. Completed studies include NCT07102095 in moderate liver impairment, NCT06378658 on food and esomeprazole effects, and earlier pharmacokinetic work. Total enrollment across the program is 511 participants.
Yes, sevabertinib is the same compound as BAY2927088. Bayer study titles use the code BAY 2927088, and related entries include BAY2927088 formulation A, formulation B_1, and a [14C]-BAY2927088 oral solution used in pharmacokinetic work. Searches for any of these names refer to the same HER2-targeted kinase inhibitor.