For Phase 1a Part A, the primary objectives are to assess safety and tolerability and to define the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of dalutrafusp alfa (formerly GS-1423) monotherapy in participants with advanced solid tumors. For Phase 1a Part B, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors. For Phase 1b Cohort 1 safety run-in, the primary objective is to assess safety and tolerability and to define the DLT and MTD or RP2D of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma. For Phase 1b Cohort 1 post safety run-in, the primary objective is to assess the preliminary efficacy of dalutrafusp alfa in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma, as assessed by the confirmed objective response rate (ORR). For Phase 1b Cohort 2, the primary objective is to assess safety and tolerability of dalutrafusp alfa monotherapy in participants with advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Administered intravenously
Chemotherapy regimen of oxaliplatin, 5-fluorouracil \[5-FU\], and leucovorin
Administered intravenously
Scottsdale Healthcare Hospitals d/b/a HonorHealth
Scottsdale, Arizona, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Mary Crowley Cancer Research
Dallas, Texas, United States
NEXT Oncology
San Antonio, Texas, United States
Phase 1a Part A: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs), Graded Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
DLT was defined as: Grade 3 thrombocytopenia with bleeding; Grade ≥ 3 febrile neutropenia; any Grade 4 hematologic laboratory abnormalities/adverse events (AEs) (except Grade 4 lymphopenia and anaemia, Grade 4 neutropenia lasting ≤ 7 days with no fever); Grade 4 non-hematologic AEs; any ≥Grade 2 uveitis, blurred vision, eye pain, and/or reduction of visual acuity that did not respond to topical therapy and did not improve to Grade 1 severity within 2 weeks of topical therapy initiation or required systemic treatment; Grade 3 non-hematologic AEs; any other non-immune-related Grade 3 AE (except any Grade 3 endocrinopathy; Grade 3 AE of tumor flare; transient \[≤ 3 days\] Grade 3 fatigue, local reactions, headache, nausea, emesis, or diarrhea and/or resolved to Grade ≤ 1; transient Grade 3 flu-like symptoms or fever); inability to receive first 2 doses of GS-1423 or \> 2-week delay in starting next cycle of therapy due to a treatment-related toxicity; Grade 5 event (death).
Time frame: Baseline up to 28 days
Phase 1a Part A: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant administered the study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore, be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Adverse events might also include pretreatment or posttreatment complications that occurred as a result of protocol-specified procedures or special situations. Preexisting events that increased in severity or change in nature during or as a consequence of participation in the study were also considered AEs. TEAEs were AEs with onset dates on or after the first dose of study drug GS-1423 and up to 30 days after permanent withdrawal of GS-1423.
Time frame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
Phase 1a Part A: Percentage of Participants With Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities
Severity was graded per NCI CTCAE v5.0. Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening or disabling, Grade 5: Death related to AE.
Time frame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
Phase 1a Part A: Percentage of Participants With Shift in Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) From Baseline to Overall Study
The Baseline value was the last available value collected on or prior to first dose of study drug. Percentages were based on participants with values available at both baseline and postbaseline. NCS = Non-clinical significance; CS = Clinical significance.
Time frame: First dose date up to permanent withdrawal of GS-1423 (maximum duration: 26.3 weeks) plus 30 days
Phase 1a Part A: Pharmacokinetic (PK) Parameter: AUCtau of GS-1423
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: Cycle 1 and Cycle 4: Day 1 (Predose, end of infusion, 2 and 6 hours post start of infusion); Days 2, 3, 5, and 8 (additionally at Day 15 in Cycle 4)
Phase 1a Part A: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs)
Time frame: Baseline, during the treatment (maximum duration: 26.3 weeks), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 4 Day 15, Cycle 6 Day 1, 30-day follow-up (30 days after discontinuation of GS-1423), post treatment follow-up (3 months)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.