PROSPECT

15 evidence topics · 5 sources

Objective

Monotherapy and first-line combination objectives

“This study will evaluate the efficacy, safety, and pharmacokinetics of tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A), and tirabrutinib in combination with one of two different high dose methotrexate based regimens (methotrexate/ temozolomide/rituximab or rituximab/methotrexate/procarbazine/ vincristine) as first line therapy in patients with newly diagnosed, treatment naïve PCNSL (Part B)” (opens the source at this quote in a new tab)

Location and study date

Part A data cutoff

“November 1, 2024” (opens the source at this quote in a new tab)

Study design

Part A trial design

“open-label phase II study” (opens the source at this quote in a new tab)

Eligibility criteria

Part A key eligibility criteria

“Patients aged ≥ 18 years on the day of consenting to the study” (opens the source at this quote in a new tab)
“Pathologic diagnosis of PCNSL” (opens the source at this quote in a new tab)
“Relapse or refractory PCNSL with at least one prior high dose methotrexate (HD-MTX) based therapy for PCNSL” (opens the source at this quote in a new tab)
“Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1 or 2” (opens the source at this quote in a new tab)

Part B newly diagnosed population

“Adults at least 18 years of age who have been newly diagnosed with PCNSL.” (opens the source at this quote in a new tab)

Treatment

Part A monotherapy

“oral tirabrutinib 480 mg” (opens the source at this quote in a new tab)
“once daily” (opens the source at this quote in a new tab)

Part B chemotherapy combinations

“MTR: Methotrexate/ temozolomide/ rituximab” (opens the source at this quote in a new tab)
“R-MPV: Rituximab/ methotrexate/ procarbazine/ vincristine” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using overall response rate as the primary endpoint

Validation as a surrogate for survival

No evidence found.

Statistical analysis description

Number of participants (Planned and analyzed)

Part A enrollment

“Forty-eight patients were enrolled.” (opens the source at this quote in a new tab)

Part B planned enrollment

“About 70 participants will be enrolled to Part B in the PROSPECT study in the United states.” (opens the source at this quote in a new tab)

Description of analysis sets

No evidence found.

Results

Participant disposition

Part A ongoing treatment at data cutoff

“At data cutoff, 13 patients (27%) remained on tirabrutinib treatment.” (opens the source at this quote in a new tab)

Baseline characteristics

Part A age

“Median age was 65.5 y (range, 34-87).” (opens the source at this quote in a new tab)

Efficacy results

Part A response and time-to-event outcomes

“With an ORR of 66.7%, CR/CRu rate of 43.8%, median DOR of 9.3 mo” (opens the source at this quote in a new tab)
“median PFS was 6.0 mo” (opens the source at this quote in a new tab)

Part B efficacy results

No evidence found.

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Part A treatment-emergent adverse events

“Incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was 56.3%.” (opens the source at this quote in a new tab)
“Two patients died of TEAEs, which were considered unrelated to study treatment.” (opens the source at this quote in a new tab)

Part A treatment-related adverse events

“grade ≥3 TRAEs were experienced by 27%, most frequently neutrophil count decreased (8%) and maculo-papular rash (6%).” (opens the source at this quote in a new tab)

Study limitations

Summary

Part A enrolled 48 participants in an open-label phase II study. The reported response and survival estimates do not establish comparative benefit against another treatment. Enrollment required an ECOG performance score of 0, 1, or 2, limiting direct applicability to participants with worse performance status. Part A monotherapy results should not be extrapolated to Part B chemotherapy combinations.