Solid Tumor
Conditions
Keywords
KRAS
Brief summary
The primary purpose of this study is to evaluate the safety and tolerability, determine the maximally tolerated dose (MTD) and/or recommended Phase 2 dose(s) (RP2D) of PT0253 in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutated advanced solid tumors as monotherapy.
Interventions
DRUGPT0253
PT0253 injection.
DRUGChemotherapy Combination 1
Intravenous infusion.
DRUGChemotherapy Combination 2
Intravenous infusion.
DRUGChemotherapy Combination 3
Intravenous infusion.
DRUGCetuximab
Intravenous infusion.
Sponsors
PAQ Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed advanced or metastatic solid malignancy 2. Participant has a pathologically documented, locally advanced or metastatic malignancy with KRAS p.G12D mutation identified through molecular testing using a Clinical Laboratory Improvement Amendments (CLIA) certified, validated institutional or commercial test. 3. Measurable disease (RECIST 1.1 Criteria). 4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. 5. Willingness to avoid pregnancy or fathering children from screening through 90 days after the last dose of study treatment.
Exclusion criteria
1. Active brain metastasis or carcinomatous meningitis. If participants have had brain metastases resected or have received radiation therapy, they may be eligible if: (1) study treatment begins at least 4 weeks from the end of brain-specific therapy, (2) residual neurological symptoms Grade less than or equal to (\<=) 2, (3) currently on stable doses of corticosteroids, and (4) pre-study brain magnetic resonance imaging (MRI) documents no new/worsening brain lesions. 2. History of any other malignancy within the past 2 years, except: * Malignancy treated with curative intent and with no known active disease present \>=2 years before enrolment and felt to be at low risk for recurrence by the investigator * Basal or squamous cell carcinoma of the skin, in situ cervical cancer, early -stage endometrial cancer that has been definitively treated, superficial bladder cancer, Gleason 6/7 treated prostate cancer, and ductal carcinoma in situ or lobular carcinoma in situ of the breast. 3. Unresolved toxicities from prior anti-cancer therapies (Common Terminology Criteria for Adverse Events \[CTCAE\] grades \>1), except for alopecia. Grade \<=2 toxicities from prior anti-tumor therapies that are considered irreversible may be allowed, provided that they are not described in the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Dose-limiting Toxicities (DLT) | Cycle 1 (Cycle length=21 days) |
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | Up to 24 months |
| Number of Participants with TEAEs Leading to Treatment Interruptions, Dose Reductions and Permanent Discontinuations | Up to 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax/C0: Maximum Blood Concentration (Cmax) and/or Concentration at Time 0 (C0) of PT0253 | Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days) | — |
| Tmax: Time to Reach Cmax of PT0253 | Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days) | — |
| AUC0-t: Area Under the Curve From time 0 to the time of the Last Quantifiable Concentration of PT0253 | Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days) | — |
| t1/2: Terminal Elimination Half-life of PT0253 | Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days) | — |
| AUC0-∞: Area Under the Curve From Time 0 Extrapolated to Infinity of PT0253 | Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days) | — |
| CL: Clearance of PT0253 | Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days) | — |
| Vd: Volume of Distribution of PT0253 | Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days) | — |
| Overall Response Rate (ORR) | Up to 24 months | ORR will be determined by radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. |
| Duration of Response (DOR) | Up to 24 months | DOR will be determined by radiographic disease assessments per RECIST 1.1. |
| Overall Survival (OS) | At 1 year | OS is defined as the time from enrollment up to death due to any cause. |
| Progression-free Survival (PFS) | At 1 year | PFS will be determined by radiographic disease assessments per RECIST 1.1. |
Countries
South Korea, United States
Contacts
CONTACTPAQ Therapeutics
Outcome results
None listed