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Also known as simlukafusp alfa
RO6874281 · 2 trials · 4 indications
| Arm | Type | Description |
|---|---|---|
| Part I Safety Run in: RO6874281 + Pembrolizumab | EXPERIMENTAL | Cohort 1.1 (CPI naive and experienced melanoma participants): Participants will receive RO6874281 in combination with Pembrolizumab every 3 weeks (Q3W) and will be observed for 2 cycles (ie: 6 weeks) in order to confirm the safety of the proposed dose and schedule that will be used in Part II of this study. Cohort 1.2 (CPI experienced melanoma participants only): Participants will receive RO6874281 in combination with Pembrolizumab via an induction and maintenance schedule for RO6874281: QW three times (D1, D8, D15) followed by Q3W dosing (D22 and subsequent). Pembrolizumab is to be administered Q3W, starting on Day 1. Participants will be observed for 2 pembrolizumab cycles (ie: 6 weeks) in order to confirm the safety of the proposed dose and schedule that will be used in Part III of this study. |
| Part II Expansion: RO6874281 + Pembrolizumab | EXPERIMENTAL | Part II will start once all participants in Part I Cohort 1.1 have completed the observation period. Approximately 34 participants will receive RO6874281 in combination with Pembrolizumab every 3 weeks (Q3W) and will be observed for 2 cycles (ie: 6 weeks). |
| Part III Expansion: RO6874281 + Pembrolizumab | EXPERIMENTAL | Part III will start once all participants in Part I Cohorts 1.1 and 1.2 have completed the observation period. Approximately 80 participants will be randomised to receive RO6874281 in combination with Pembrolizumab in either a Q3W or QW/Q3W schedule. |
| Part A: RO6874281 Monotherapy | EXPERIMENTAL | Dose Escalation: RO6874281 will be administered as an intravenous (IV) infusion. The starting dose regimen of RO6874281 as a single agent will be 5 milligrams (mg) once weekly (QW). Different regimens may be explored based on the emerging safety, PK, and PD data of RO6874281 and may be tested in parallel. Participants will be treated with RO6874281 until disease progression, unacceptable toxicities, or withdrawal of consent. Participants may continue treatment with RO6874281 for a maximum of 24 months. |
| Part B: RO6874281 in Combination with Trastuzumab | EXPERIMENTAL | Dose Escalation: RO6874281 will be administered as an IV infusion. RO6874281 will be administered QW for the first 4 administrations, then Q2W. The standard dose for trastuzumab will be a loading dose of 6 milligrams per kilogram (mg/kg) followed by a maintenance dose of 4 mg/kg from Cycle 2 in a Q2W regimen. Different regimens may be explored based on the emerging safety, PK, and PD data of RO6874281 and may be tested in parallel. Participants will be treated with RO6874281 in combination with trastuzumab until disease progression, unacceptable toxicities, or withdrawal of consent. Participants may continue treatment with RO6874281 in combination with trastuzumab for a maximum of 24 months. |
| Part C: RO6874281 in Combination with Cetuximab | EXPERIMENTAL | RO6874281 will be administered as an IV infusion. The starting dose regimen of RO6874281 in combination with cetuximab will be 5 mg QW for the first 4 administrations, then Q2W. Cetuximab will be administered Q2W at 500 milligrams per square meter (mg/m\^2). Different regimens may be explored based on the emerging safety, PK, and PD data of RO6874281 and may be tested in parallel. Participants will be treated with RO6874281 in combination with cetuximab until disease progression, unacceptable toxicities, or withdrawal of consent. Participants may continue treatment with RO6874281 in combination with cetuximab for a maximum of 24 months. Extension Phase: The MTD for RO6874281 was determined to be 10mg and therefore patients in the extension will be treated with 10mg RO6874281. Cetuximab and R06874281 will be administered weekly during induction phase (cycle 1 and cycle 2). Both IMPs will be administered Q2W starting in cycle 3. |
| Name | Type | Description |
|---|---|---|
| RO6874281 | DRUG | Part I Safety Run in: Cohort 1.1: RO6874281 will be administered by intravenous (IV) infusion; 10 mg (Q3W) every 3 weeks and will be observed over 2 administration cycles (i.e. 6 weeks) in order to confirm the safety of the proposed dose and schedule that will be used in Part II of this study. Cohort 1.2: RO6874281 will be administered by IV infusion via an induction and maintenance phase; 10 mg (QW) every week for 3 weeks followed by 10 mg (Q3W) every 3 weeks and will be observed over 2 administration cycles (6 weeks) to confirm safety of the proposed dose and schedule to be used in Part III of this study. Part II Expansion: RO6874281 will be administered by IV infusion; 10 mg (Q3W) every 3 weeks (or lower dose level depending on Part I Cohort 1.1 outcome). Part III Expansion: RO6874281 will be administered by IV infusion; 10 mg (QW) every week or 10mg (Q3W) every 3 weeks (or lower dose level depending on Part I Cohorts 1.1 and 1.2 outcomes) in either a Q3W or QW/Q3W schedule. |
| Pembrolizumab | DRUG | Part I Safety Run in (Cohorts 1.1 and 1.2): Pembrolizumab will be administered by IV; 200 mg Q3W and will be observed over 2 administration cycles (i.e. 6 weeks). Part II Expansion: Pembrolizumab will be administered by IV; 200 mg Q3W (or lower dose level depending on Part I Cohort 1.1 outcome) Part III Expansion: Pembrolizumab will be administered by IV; 200 mg Q3W (or lower dose level depending on Part I Cohorts 1.1 and 1.2 outcomes) |
| Trastuzumab | DRUG | Trastuzumab will be administered as per the schedule specified under arm description. |
| Cetuximab | DRUG | Cetuximab will be administered as per the schedule specified under arm description. |
Inclusion Criteria: 1. Histologically confirmed unresectable stage III or stage IV cutaneous or mucosal melanoma (AJCC v8.0). 2. Participants need to have known BRAF status. 3. CPI naïve melanoma population: Participants with unresectable stage III or stage IV cutaneous or mucosal melanoma who have...
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RO6874281 is an investigational cancer therapy being studied for metastatic melanoma and other solid tumors. It has been tested in adults with advanced or metastatic melanoma, as well as in solid tumors including breast cancer and head and neck cancer. It is not an approved treatment and remains in clinical development.
RO6874281 is developed by Roche Holding AG, which trades on the OTC market under the ticker RHHBY. Roche sponsored the clinical program evaluating the agent in metastatic melanoma and solid tumors.
RO6874281 is in Phase 1 clinical development. Both of its recorded Phase 1 studies have been completed, and no active trials are currently listed. The drug is investigational and has not been approved by the FDA for any indication.
RO6874281 has been evaluated in two completed Phase 1 trials. NCT03875079 tested it in combination with pembrolizumab in advanced or metastatic melanoma, enrolling 83 participants. NCT02627274 studied it as a single agent and in combination with trastuzumab or cetuximab in solid tumors, enrolling 134 participants.
Yes. RO6874281 was studied in combination with pembrolizumab in advanced or metastatic melanoma in trial NCT03875079. A separate trial, NCT02627274, evaluated it as a single agent and in combination with trastuzumab or cetuximab in solid tumors, including breast cancer and head and neck cancer.
The RO6874281 clinical program enrolled 134 participants in its solid tumor study, NCT02627274, and 83 participants in the metastatic melanoma study, NCT03875079. Both trials were Phase 1, controlled, and included adults aged 18 years and older across sites in North America, Europe, and Australia.