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Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in T-cell Lymphoma

A Phase I/Ib, Dose Escalation Study to Evaluate Safety and Efficacy of RP6530, a Dual PI3K δ/γ Inhibitor, in Patients With Relapsed or Refractory T-cell Lymphoma

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02567656
Enrollment
58
Registered
2015-10-05
Start date
2015-09-30
Completion date
2018-12-10
Last updated
2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma, T-Cell, Cutaneous, Lymphoma, T-Cell, Peripheral

Keywords

CTCL, PTCL, RP6530

Brief summary

The purpose of this study is to evaluate the safety, PK and efficacy of RP6530, a dual PI3K delta/gamma inhibitor in patients with relapsed and refractory T-cell Lymphoma.

Detailed description

Safety: Treatment-Emergent AE; Treatment-Related AE, SAE and Clinical significant AE; Dose Limiting Toxicities (DLT). PK: Peak Plasma Concentration (Cmax), Area under the plasma concentration versus time curve (AUC), Time of Maximum concentration observed (Tmax). Efficacy: Overall Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS) and Duration of Response.

Interventions

DRUGRP6530

Tablet starting at 200 mg

Sponsors

Rhizen Pharmaceuticals SA
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Histologically confirmed T cell Non-Hodgkin Lymphoma (T-NHL) * Refractory to or relapsed after at least 1 prior treatment line. * ECOG performance status ≤2 * Patients must be ≥18 years of age * Able to give a written informed consent.

Exclusion criteria

* Any cancer therapy in the last 3 weeks or limited palliative radiation \<2 weeks * Patients with HBV, HCV or HIV infection * Previous therapy with GS-1101 (CAL-101, Idelalisib), IPI-145 (Duvelisib), TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib) in last 6 months * Patients on immunosuppressive therapy including systemic corticosteroids. * Patients with known history of liver disorders. * Patients with uncontrolled Diabetes Type I or Type II * Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study. * Women who are pregnant or lactating.

Design outcomes

Primary

MeasureTime frameDescription
Safety of RP653028 daysNumber of participants with Treatment-Related Adverse Events as Assessed by CTACE v4.0

Secondary

MeasureTime frameDescription
Overall Response Rate (ORR) With RP65308 monthsORR is defined as sum of CR and PR rates, Response assessment for PTCL based on IWG criteria (Cheson 2007) and CTCL on mSWAT/Global assessment (ISCL/EORTC guideline).
Duration of Response (DOR) With RP653024 monthsThe time period from the response achieved in patient until the disease progression.
Peak Plasma Concentration (Cmax)Day 1 of Cycle 1Peak Plasma Concentration (Cmax) of RP6530

Countries

United States

Participant flow

Participants by arm

ArmCount
Dose escalation_Cohort 1_200 mg
RP6530 administered 200 mg orally twice a day.
4
Dose escalation_Cohort 2_400 mg
RP6530 administered 400 mg orally twice a day.
4
Dose escalation_Cohort 3_800 mg (Fasting)
RP6530 administered 800 mg orally twice a day under fasting condition
5
Dose escalation_Cohort 4_800 mg (Fed)
RP6530 administered 800 mg orally twice a day under fed condition
6
Dose expansion_PTCL_800 mg (Fasting)
RP6530 administered 800 mg orally twice a day under fasting condition
19
Dose expansion_CTCL_800 mg (Fasting)
RP6530 administered 800 mg orally twice a day under fasting condition
20
Total58

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Overall StudyPremature discontinuation due to PD112000

Baseline characteristics

CharacteristicDose escalation_Cohort 1_200 mgTotalDose expansion_CTCL_800 mg (Fasting)Dose expansion_PTCL_800 mg (Fasting)Dose escalation_Cohort 4_800 mg (Fed)Dose escalation_Cohort 3_800 mg (Fasting)Dose escalation_Cohort 2_400 mg
Age, Continuous63.45 Years67.07 Years67.07 Years63.95 Years65.86 Years67.89 Years65.03 Years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants0 Participants1 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants8 Participants4 Participants4 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
4 Participants49 Participants16 Participants14 Participants6 Participants5 Participants4 Participants
Region of Enrollment
United States
4 participants58 participants20 participants19 participants6 participants5 participants4 participants
Sex: Female, Male
Female
3 Participants28 Participants13 Participants7 Participants1 Participants2 Participants2 Participants
Sex: Female, Male
Male
1 Participants30 Participants7 Participants12 Participants5 Participants3 Participants2 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
deaths
Total, all-cause mortality
0 / 41 / 41 / 51 / 63 / 191 / 20
other
Total, other adverse events
4 / 43 / 45 / 55 / 611 / 1917 / 20
serious
Total, serious adverse events
0 / 40 / 40 / 50 / 63 / 193 / 20

Outcome results

Primary

Safety of RP6530

Number of participants with Treatment-Related Adverse Events as Assessed by CTACE v4.0

Time frame: 28 days

Population: DLT assessment performed in patients who participated in dose escalation phase; A toxicity will be considered dose-limiting if it occurs during the first cycle (4-weeks) treatment with Tenalisib and is considered related to Tenalisib.

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
Dose escalation_Cohort 1_200 mgSafety of RP6530No.of Participants without Dose Limiting Toxicitie4 Participants
Dose escalation_Cohort 1_200 mgSafety of RP6530No.of Participants with Dose Limiting Toxicities0 Participants
Dose escalation_Cohort 2_400 mgSafety of RP6530No.of Participants with Dose Limiting Toxicities0 Participants
Dose escalation_Cohort 2_400 mgSafety of RP6530No.of Participants without Dose Limiting Toxicitie4 Participants
Dose escalation_Cohort 3_800 mg (Fasting)Safety of RP6530No.of Participants with Dose Limiting Toxicities0 Participants
Dose escalation_Cohort 3_800 mg (Fasting)Safety of RP6530No.of Participants without Dose Limiting Toxicitie5 Participants
Dose escalation_Cohort 4_800 mg (Fed)Safety of RP6530No.of Participants with Dose Limiting Toxicities2 Participants
Dose escalation_Cohort 4_800 mg (Fed)Safety of RP6530No.of Participants without Dose Limiting Toxicitie4 Participants
Dose expansion_PTCL_800 mg (Fasting)Safety of RP6530No.of Participants without Dose Limiting Toxicitie0 Participants
Dose expansion_PTCL_800 mg (Fasting)Safety of RP6530No.of Participants with Dose Limiting Toxicities0 Participants
Dose expansion_CTCL_800 mg (Fasting)Safety of RP6530No.of Participants with Dose Limiting Toxicities0 Participants
Dose expansion_CTCL_800 mg (Fasting)Safety of RP6530No.of Participants without Dose Limiting Toxicitie0 Participants
Secondary

Duration of Response (DOR) With RP6530

The time period from the response achieved in patient until the disease progression.

Time frame: 24 months

Population: Duration of Response (DoR) is defined as the time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death. Overall number of Participants analyzed for DoR will be the participants who met response as CR or PR

ArmMeasureValue (MEDIAN)
Dose escalation_Cohort 1_200 mgDuration of Response (DOR) With RP6530147 Days
Dose escalation_Cohort 2_400 mgDuration of Response (DOR) With RP653072 Days
Dose escalation_Cohort 3_800 mg (Fasting)Duration of Response (DOR) With RP6530313 Days
Dose escalation_Cohort 4_800 mg (Fed)Duration of Response (DOR) With RP653099 Days
Dose expansion_PTCL_800 mg (Fasting)Duration of Response (DOR) With RP6530141 Days
Dose expansion_CTCL_800 mg (Fasting)Duration of Response (DOR) With RP6530307 Days
Secondary

Overall Response Rate (ORR) With RP6530

ORR is defined as sum of CR and PR rates, Response assessment for PTCL based on IWG criteria (Cheson 2007) and CTCL on mSWAT/Global assessment (ISCL/EORTC guideline).

Time frame: 8 months

Population: Patients were considered for efficacy analysis as per protocol only if they had one post treatment efficacy assessment at C3D1

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Dose escalation_Cohort 1_200 mgOverall Response Rate (ORR) With RP65301 Participants
Dose escalation_Cohort 2_400 mgOverall Response Rate (ORR) With RP65302 Participants
Dose escalation_Cohort 3_800 mg (Fasting)Overall Response Rate (ORR) With RP65302 Participants
Dose escalation_Cohort 4_800 mg (Fed)Overall Response Rate (ORR) With RP65302 Participants
Dose expansion_PTCL_800 mg (Fasting)Overall Response Rate (ORR) With RP65304 Participants
Dose expansion_CTCL_800 mg (Fasting)Overall Response Rate (ORR) With RP65305 Participants
Secondary

Peak Plasma Concentration (Cmax)

Peak Plasma Concentration (Cmax) of RP6530

Time frame: Day 1 of Cycle 1

Population: Peak Plasma Concentration (Cmax) of RP6530 at Cycle 1 day 1

ArmMeasureValue (MEAN)Dispersion
Dose escalation_Cohort 1_200 mgPeak Plasma Concentration (Cmax)1297.65 ng/mLStandard Deviation 622.81
Dose escalation_Cohort 2_400 mgPeak Plasma Concentration (Cmax)2196.65 ng/mLStandard Deviation 676.45
Dose escalation_Cohort 3_800 mg (Fasting)Peak Plasma Concentration (Cmax)3995.68 ng/mLStandard Deviation 1392.74
Dose escalation_Cohort 4_800 mg (Fed)Peak Plasma Concentration (Cmax)2668.05 ng/mLStandard Deviation 1713.17

Source: ClinicalTrials.gov · Data processed: Feb 28, 2026