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Also known as RO5503781
Idasanutlin · 4 trials · 2 indications
| Arm | Type | Description |
|---|---|---|
| Treatment Sequence 1: ABCD | EXPERIMENTAL | Treatment A: A single dose of the current idasanutlin tablet A formulation (reference variant) on Cycle 1, Day 1 (one cycle is 28 days). Treatment B: A single dose of new idasanutlin tablet B (to investigate BE compared to tablet A) on Cycle 1, Day 8. Treatment C: A single dose of new idasanutlin tablet C (to investigate rBA compared to tablet A; rBA 1) on Cycle 1, Day 15. Treatment D: A single dose of new idasanutlin tablet D (to investigate rBA compared to tablet A; rBA 2) on Cycle 1, Day 22. Following completion of the BE/rBA cycle (Cycle 1), participants may continue to receive optional treatment cycles of the reference tablet formulation of idasanutlin, as specified in the Optional Treatment Extension Arm description. |
| Treatment Sequence 2: ABDC | EXPERIMENTAL | Treatment A: A single dose of the current idasanutlin tablet A formulation (reference variant) on Cycle 1, Day 1 (one cycle is 28 days). Treatment B: A single dose of new idasanutlin tablet B (to investigate BE compared to tablet A) on Cycle 1, Day 8. Treatment D: A single dose of new idasanutlin tablet D (to investigate rBA compared to tablet A; rBA 2) on Cycle 1, Day 15. Treatment C: A single dose of new idasanutlin tablet C (to investigate rBA compared to tablet A; rBA 1) on Cycle 1, Day 22. Following completion of the BE/rBA cycle (Cycle 1), participants may continue to receive optional treatment cycles of the reference tablet formulation of idasanutlin, as specified in the Optional Treatment Extension Arm description. |
| Treatment Sequence 3: BACD | EXPERIMENTAL | Treatment B: A single dose of new idasanutlin tablet B (to investigate BE compared to tablet A) on Cycle 1, Day 1 (one cycle is 28 days). Treatment A: A single dose of the current idasanutlin tablet A formulation (reference variant) on Cycle 1, Day 8. Treatment C: A single dose of new idasanutlin tablet C (to investigate rBA compared to tablet A; rBA 1) on Cycle 1, Day 15. Treatment D: A single dose of new idasanutlin tablet D (to investigate rBA compared to tablet A; rBA 2) on Cycle 1, Day 22. Following completion of the BE/rBA cycle (Cycle 1), participants may continue to receive optional treatment cycles of the reference tablet formulation of idasanutlin, as specified in the Optional Treatment Extension Arm description. |
| Treatment Sequence 4: BADC | EXPERIMENTAL | Treatment B: A single dose of new idasanutlin tablet B (to investigate BE compared to tablet A) on Cycle 1, Day 1 (one cycle is 28 days). Treatment A: A single dose of the current idasanutlin tablet A formulation (reference variant) on Cycle 1, Day 8. Treatment D: A single dose of new idasanutlin tablet D (to investigate rBA compared to tablet A; rBA 2) on Cycle 1, Day 15. Treatment C: A single dose of new tablet C (to investigate rBA compared to tablet A; rBA 1) on Cycle 1, Day 22. Following completion of the BE/rBA cycle (Cycle 1), participants may continue to receive optional treatment cycles of the reference tablet formulation of idasanutlin, as specified in the Optional Treatment Extension Arm description. |
| Optional Treatment Extension Arm | EXPERIMENTAL | Following completion of the BE/rBA cycle (Cycle 1), participants who have no clinically defined progressive disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and who recover from any prior treatment toxicity to Grade \</=1 may enter the optional treatment extension phase. Participants will receive 200 mg idasanutlin orally (200-mg tablet reference formulation) daily for 5 days, followed by 23 days of rest. This extension phase will continue for additional 28-day cycles or until disease progression or unacceptable toxicity is observed. |
| Idasanutlin | EXPERIMENTAL | On Day 1, 300 milligram (mg) idasanutlin tablet orally and 100 mg \[14C\]-radiolabeled idasanutlin capsule orally (2, 50 mg capsules containing approximately 100 microcurie of radioactivity). After 5 hours and 45 minutes of the oral dose, 100 microgram (mcg) of \[13C\]-radiolabeled idasanutlin will be administered over a 15-minute intravenous (IV) infusion. On Day 11, idasanutlin matching placebo aqueous dispersion orally and approximately after 1 hour, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. On Day 19, 400 mg idasanutlin tablet will be administered orally in the form of an aqueous dispersion. Participants, who are eligible to enter in optional treatment extension phase, will continue treatment with idasanutlin 200 mg tablet orally once daily for 5 days, and no treatment during 23 days of 28-day cycle, until the development of progressive disease, unacceptable toxicity, consent withdrawal or any other criteria for removal. |
| Extension | EXPERIMENTAL | - |
| Part 1: Drug-drug interaction | EXPERIMENTAL | - |
| Part 2: Relative bioavailability | EXPERIMENTAL | - |
| Part 3: Food effect | EXPERIMENTAL | - |
| Schedule A: RO5503781 QW | EXPERIMENTAL | Participants will receive multiple ascending doses of RO5503781 orally once weekly (QW) x 3 followed by 13 days of rest in a 28 days cycle. |
| Schedule B: RO5503781 QD | EXPERIMENTAL | Participants will receive multiple ascending doses of RO5503781 orally QD x 5 followed by 13 days of rest in a 28 days cycle. |
| Name | Type | Description |
|---|---|---|
| Idasanutlin | DRUG | Participants will receive one 300-mg dose of each of the four different oral tablet formulations of idasanutlin (tablet A \[reference\], B, C, D) during Cycle 1, in the order specified for their assigned treatment arm (Treatment Sequence 1-4). Participants who enter the optional treatment extension phase will receive the reference tablet formulation of idasanutlin, as specified in the Optional Treatment Extension Arm description. |
| Placebo | DRUG | Placebo matching to idasanutlin aqueous dispersion will be administered orally on Day 11. |
| [13C]-radiolabeled Idasanutlin | DRUG | \[13C\]-radiolabeled idasanutlin 100 mcg will be administered as IV infusion over 15-minute on Day 1. |
| [14C]-radiolabeled Idasanutlin | DRUG | \[14C\]-radiolabeled idasanutlin 100 mg capsule (2, 50 mg capsules containing approximately 100 microcurie of radioactivity) will be administered orally on Day 1. |
| RO5503781 | DRUG | Single dose on Day 1 (high fat, low fat, or fasted), Day 10 (fasted, low fat, or high fat), and Day 19 (low fat, fasted, or high fat) in a crossover design |
| posaconazole | DRUG | Multiple doses Days 8-14 |
Inclusion Criteria: * Participant must have histologically or cytologically confirmed advanced malignancies, except all forms of leukemia and lymphoma, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the participant * Measureable or...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
Idasanutlin is an investigational small molecule developed by Roche Holding AG (ticker RHHBY) for the treatment of solid tumors. It is an oncology candidate that has been studied in Phase 1 clinical trials. It is not an approved therapy and remains in clinical development.
Idasanutlin targets MDM2 and TP53. It is an inhibitor that acts on the MDM2 protein, which regulates the tumor suppressor TP53. By inhibiting MDM2, the drug is designed to affect the MDM2-TP53 interaction in tumor cells. This mechanism is being studied in solid tumors.
Idasanutlin is developed by Roche Holding AG, which trades under the ticker RHHBY. Roche is the sponsor of the clinical studies evaluating the drug in patients with solid tumors. The compound is an investigational oncology asset in the company's pipeline.
Idasanutlin is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. The Phase 1 program in solid tumors has completed, with two completed trials and no active trials currently listed.
Idasanutlin has been evaluated in two completed Phase 1 trials in solid tumors. NCT03362723 studied the bioequivalence or relative bioavailability of three new tablet variants in 48 participants in the United States and Canada. NCT02828930 examined excretion balance, pharmacokinetics, metabolism and absolute oral bioavailability in 8 participants in Hungary.
The two completed Phase 1 trials of Idasanutlin in solid tumors enrolled a total of 56 participants. NCT03362723 enrolled 48 participants, and NCT02828930 enrolled 8 participants. Both studies required participants to be at least 18 years old and did not use healthy volunteers.