Advanced Solid Malignancies Clinical Trial
Official title:
A First-In-Human, Phase 1/2 Study Of CFI-402411, a Hematopoietic Progenitor Kinase-1 (HPK1) Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Malignancies
The purpose of this study is to test the safety of an investigational drug called CFI-402411 alone and in combination with pembrolizumab and to study its effects in patients with advanced solid tumors who have progressed following previous therapies.
Status | Recruiting |
Enrollment | 170 |
Est. completion date | December 2024 |
Est. primary completion date | November 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Key Inclusion Criteria: Study-Wide Eligibility (Across All Study Parts): 1. Age > 18 years old 2. Have progressed after = 1, but no more than 3 regimens of systemic therapies for recurrent / metastatic disease. 3. Subjects must have measurable disease. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Part A1: Monotherapy Dose Escalation Inclusion Criteria 1. Histological or cytological confirmation of advanced solid malignancy that is refractory to or not a candidate for current standard treatment(s) and for whom no standard therapy is available. Part A2: Biomarker-Focused Monotherapy Backfills Inclusion Criteria 1. Histological or cytological confirmation of one of the advanced cancers listed below; - NSCLC - SCLC - cutaneous melanoma - Merkel cell carcinoma - squamous cell carcinoma of head and neck, anal canal, or skin - urothelial cancer - clear cell or non-clear cell renal cell carcinoma - triple negative breast cancer - endometrial cancer (regardless of MSI status) - cervical cancer - gastroesophageal cancer - hepatocellular cancer - any histology if known to be microsatellite-instability high (MSI-H) 2. Tumors must be refractory to or not a candidate for current standard treatment(s) and for whom no standard therapy exists. Part A3: Monotherapy Expansion Inclusion Criteria 1. Histological or cytological confirmation of one of the advanced cancers listed below; - NSCLC cancer any histology - SCLC - cutaneous melanoma - Merkel cell carcinoma - squamous cell carcinoma of head and neck, anal canal, or skin - urothelial cancer - clear cell or non-clear cell renal cell carcinoma - triple negative breast cancer - endometrial cancer (regardless of MSI status) - cervical cancer - gastroesophageal cancer - hepatocellular - any histology if known to be microsatellite-instability high (MSI-H) 2. Tumors must be refractory to or subjects intolerant of current standard treatment(s) and for whom no standard therapies are available. 3. Optional biopsies: Subjects that consent to optional fresh tumor biopsies must have at least one non-target soft tissue tumor lesion that can be biopsied. Part B1: CFI-402411 in Combination with Pembrolizumab Dose Escalation Inclusion Criteria 1. Subjects must be deemed eligible by the Investigator to receive pembrolizumab. 2. Histological or cytological confirmation of one of the advanced cancers listed below (list may vary in each country, USA shown here); - NSCLC cancer any histology - SCLC - cutaneous melanoma - Merkel cell carcinoma - squamous cell carcinoma of head and neck, anal canal, or skin - urothelial cancer - clear cell or non-clear cell renal cell carcinoma - triple negative breast cancer - endometrial cancer (regardless of MSI status) - cervical cancer - gastroesophageal cancer - hepatocellular cancer - any histology if known to be microsatellite-instability high (MSI-H) Tumors must be refractory to or subjects intolerant of current standard treatment(s) or for whom no standard therapy is available. Part B2: CFI-402411 in Combination with Pembrolizumab Expansion Inclusion Criteria 1. Subjects must be deemed eligible by the Investigator to receive pembrolizumab 2. Histological or cytological confirmation of one of the advanced cancers listed below (list may vary in each country, USA shown here); - non-small cell lung cancer any histology - SCLC - cutaneous melanoma - Merkel Cell carcinoma - squamous cell carcinoma of head and neck, anal canal, or skin - urothelial cancer - clear cell or non-clear cell renal cell carcinoma - triple negative breast cancer - endometrial cancer (regardless of MSI status) - gastroesophageal cancer - hepatocellular cancer - any histology if known to be microsatellite-instability high (MSI-H) 3. Tumors must be refractory to or subjects intolerant of current standard non-IO treatment(s) or for whom no standard therapy is available. Key Exclusion Criteria: Study-Wide Eligibility (Across All Study Parts) Subjects will be excluded from the study if any of the following criteria is met; 1. Previous treatment with an HPK1 inhibitor in other clinical trials. 2. Diagnosis of autoimmune-based disease or clinically significant auto-immune disorders. 3. Have symptomatic congestive heart failure, active angina pectoris or recent myocardial infarction (within 6 mos). 4. Have chronic atrial fibrillation. 5. Known central nervous system metastasis. 6. Stroke or transient ischemic attack, or other ischemic events or thromboembolic events within 3 months of study enrollment. 7. A history of QTc prolongation or a marked baseline prolongation of QT/QTc interval or a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). |
Country | Name | City | State |
---|---|---|---|
Canada | Cross Cancer Institute | Edmonton | Alberta |
Canada | The Ottawa Hospital | Ottawa | Ontario |
Canada | Princess Margaret Cancer Centre | Toronto | Ontario |
Hong Kong | Prince of Wales Hospital | Sha Tin | |
United States | Virginia Cancer Specialist | Fairfax | Virginia |
United States | START - Mid-West | Grand Rapids | Michigan |
United States | MD Anderson | Houston | Texas |
United States | University of California San Diego | La Jolla | California |
United States | The Angeles Clinic | Los Angeles | California |
United States | SCRI - Nashville | Nashville | Tennessee |
United States | Yale Cancer Center | New Haven | Connecticut |
United States | START - San Antonio | San Antonio | Texas |
United States | Florida Cancer Specialists | Sarasota | Florida |
Lead Sponsor | Collaborator |
---|---|
Treadwell Therapeutics, Inc | TIO Discovery Engine |
United States, Canada, Hong Kong,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To assess the incidence of adverse events of CFI-402411 as a single agent and at the recommended phase 2 dose (RP2D). | The number of subjects who experience an adverse event that was possibly related to study drug. | 48 months | |
Primary | To assess the incidence of adverse events with CFI-402411 in combination with pembrolizumab and at the RP2D. | The number of subjects who experience an adverse event that was possibly related to study drug. | 48 months | |
Primary | To examine best overall response rate in subjects treated at multiple dose levels of CFI-402411. | Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category. | 48 months | |
Primary | To examine progression free survival in subjects treated at multiple dose levels of CFI-402411. | Time from first dose to disease progression or death whichever occurs first will be calculated and summarized for all patients by dose cohort and overall. | 48 months | |
Secondary | To identify the maximum tolerated dose of single agent CFI-402411 alone and in combination with pembrolizumab. | Safety tables and pharmacokinetic tables will be assessed. | 48 months | |
Secondary | To further assess the incidence of adverse events of CFI-402411. | The number of subjects who experience an adverse event that was possibly related to study drug. | 48 months | |
Secondary | To assess best overall response of CFI-402411 monotherapy and in combination with pembrolizumab. | Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category. | 48 months | |
Secondary | To assess overall response rates of CFI-402411 monotherapy and in combination with pembrolizumab. | For all subjects the overall response rates of complete response and partial response will be calculated and summarized by dose cohort and overall. | 48 months | |
Secondary | To assess overall survival of CFI-402411 monotherapy and in combination with pembrolizumab. | The time from first dose until the date of death from any cause will be calculated and summarized for all patients by dose cohort and overall. | 48 months | |
Secondary | To assess progression free survival of CFI-402411 monotherapy and in combination with pembrolizumab. | Time from first dose to disease progression or death whichever occurs first will be calculated and summarized for all patients by dose cohort and overall. | 48 months | |
Secondary | To assess duration of response of CFI-402411 monotherapy and in combination with pembrolizumab. | The time from the first objective response to the time of documented disease progression or death due to any cause, whichever occurs first, will be calculated and summarized for all patients by dose cohort and overall. | 48 months | |
Secondary | To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through AUC. | Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group. | 48 months | |
Secondary | To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Cmax. | Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group. | 48 months | |
Secondary | To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Tmax. | Tmax will be assessed by the time to achieve maximum plasma concentration and will be tabulated by dose group. | 48 months | |
Secondary | To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab though Cmin. | Cmin will be calculated through the measured pre-dose plasma concentration and tabulated by dose group. | 48 months | |
Secondary | To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through T1/2. | Elimination half life will be calculated and tabulated by dose group. | 48 months | |
Secondary | To evaluate the effect of CFI-402411 treatment on immune- or disease related biomarkers. | The effects of CFI-402411 on pharmacodynamic biomarkers (cytokine levels) will be assessed by percent changes from baseline. | 48 months |
Status | Clinical Trial | Phase | |
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