Advanced Solid Tumor
Conditions
Brief summary
The primary purpose of this study is to assess the safety and tolerability of RP-6306 with FOLFIRI in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD), identify a recommended phase 2 dose (RP2D) and preferred schedule, and assess preliminary anti-tumor activity.
Detailed description
To assess the safety and tolerability of RP-6306 in combination with FOLFIRI in patients with eligible, advanced solid tumors. Incidence and severity of treatment-emergent adverse events (TEAEs), laboratory assessments, vital signs, electrocardiograms (ECGs), and use of concomitant medications. The Sponsor of the study has changed from 'Repare Therapeutics' to 'Debiopharm International SA' in the United States.
Interventions
RP-6306 (Oral) in combination with FOLFIRI (IV)
Sponsors
Repare Therapeutics
Debiopharm International SA
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation and expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female and ≥18 years-of-age at the time of signature of the informed consent * Confirmed advanced solid tumors resistant or refractory to standard treatment * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. * All patients must have locally advanced or metastatic CRC, GI, or esophageal cancer(s) and radiographic evidence of progressing disease. * Measurable disease as per RECIST v1.1 * Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible * Acceptable hematologic and organ function at screening * Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.
Exclusion criteria
* Inability to swallow and retain oral medications. * Chemotherapy or small molecule antineoplastic agent given within 21 days or \<5 half- lives, whichever is shorter, prior to first dose of study treatment. * History or current condition, therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment. * Patients who are pregnant or breastfeeding * Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the participating patient's safety. * Major surgery within 4 weeks prior to first study treatment dose. * Uncontrolled, symptomatic brain metastases. * Uncontrolled high blood pressure * Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness. * Moderate or severe hepatic impairment * Cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥Class 2 * Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of RP 6306 in Combination With FOLFIRI | Start of treatment to 30 days post last dose. up to 1.5 years | Incidence of grade 3 and above Treatment Related Emergent Adverse Events (TRAEs) |
| Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | During 28 days (2 cycles) from the initiation of the study treatment | Evaluation of dose-limiting toxicities (DLTs) at or below a frequency of 25%. |
Countries
Canada, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 40 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI 40 mg QD oral (PO) lunresertib daily in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 2 |
| 120 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI 120 mg QD oral (PO) lunresertib daily in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 3 |
| 180 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI 180 mg QD oral (PO) lunresertib daily in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 9 |
| 240 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI 240 mg QD oral (PO) lunresertib daily in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 4 |
| 60 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI 60 mg BID oral (PO) lunresertib daily in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 7 |
| 80 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI 80 mg BID oral (PO) lunresertib daily in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 3 |
| 80 mg BID RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI 80 mg BID oral (PO) lunresertib 3 days on and 4 days off in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 4 |
| 120 mg QD RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI 120 mg BID oral (PO) lunresertib 3 days on and 4 days off in combination with 180 mg/m2 intravenous (IV) irinotecan given over 30 to 90 minutes, 400 mg/m2 IV leucovorin given over 30 to 90 minutes with irinotecan, and 400 mg/m2 IV fluorouracil bolus after leucovorin, then 2400 mg/m2 IV continuous IV of fluorouracil over 46 hours (Days 1 and 2) of each 14-day cycle | 6 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 3 | 3 | 2 | 2 | 1 | 1 | 3 |
| Overall Study | Other Reasons | 0 | 0 | 2 | 0 | 0 | 2 | 1 | 1 |
| Overall Study | Sponsor Decision to Terminate Study | 0 | 0 | 1 | 0 | 4 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 | 1 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 120 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | 180 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | 240 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | 60 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI | 80 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI | 80 mg BID RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI | 40 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | 120 mg QD RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized Age | 55 years | 58 years | 66 years | 68 years | 42 years | 44 years | 51 years | 61 years | 55.5 years |
| Gene Type CCNE1 | 0 participants | 4 participants | 0 participants | 2 participants | 0 participants | 2 participants | 0 participants | 4 participants | 12 participants |
| Gene Type FBXW7 | 3 participants | 5 participants | 4 participants | 5 participants | 3 participants | 2 participants | 2 participants | 2 participants | 26 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 0 Participants | 4 Participants | 25 Participants |
| Region of Enrollment Canada | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Spain | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants |
| Region of Enrollment United States | 3 Participants | 4 Participants | 1 Participants | 6 Participants | 0 Participants | 2 Participants | 2 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 2 | 3 / 3 | 3 / 9 | 2 / 4 | 2 / 7 | 1 / 3 | 1 / 4 | 3 / 6 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 9 / 9 | 4 / 4 | 7 / 7 | 3 / 3 | 4 / 4 | 6 / 6 |
| serious Total, serious adverse events | 1 / 2 | 2 / 3 | 5 / 9 | 3 / 4 | 3 / 7 | 1 / 3 | 2 / 4 | 2 / 6 |
Outcome results
Primary
Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI
Evaluation of dose-limiting toxicities (DLTs) at or below a frequency of 25%.
Time frame: During 28 days (2 cycles) from the initiation of the study treatment
Population: DLT evaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 40 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 0 Participants |
| 120 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 0 Participants |
| 180 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 0 Participants |
| 240 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 2 Participants |
| 60 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 0 Participants |
| 80 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 0 Participants |
| 80 mg BID RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 2 Participants |
| 120 mg QD RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI | Recommended Phase 2 Dose (RP2D) and Schedule of RP-6306 in Combination With FOLFIRI | 1 Participants |
Primary
Safety and Tolerability of RP 6306 in Combination With FOLFIRI
Incidence of grade 3 and above Treatment Related Emergent Adverse Events (TRAEs)
Time frame: Start of treatment to 30 days post last dose. up to 1.5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 40 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 1 Participants |
| 120 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 1 Participants |
| 180 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 6 Participants |
| 240 mg QD RP-6306 (Lunresertib) Daily + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 3 Participants |
| 60 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 0 Participants |
| 80 mg BID RP-6306 (Lunresertib) Daily + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 1 Participants |
| 80 mg BID RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 2 Participants |
| 120 mg QD RP-6306 (Lunresertib) 3 Days on and 4 Days Off + FOLFIRI | Safety and Tolerability of RP 6306 in Combination With FOLFIRI | 4 Participants |