Clinical trial NCT04521413: Safety and Efficacy Study of CFI-402411 in Subjects With Advanced Solid Malignancies
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Malignancies
Keywords: advanced tumors
pembro
keytruda
pembrolizumab
2411
CFI-402411
first in human
first-in-human
hematopoietic progenitor kinase-1 inhibitor
HPK1
advanced solid malignancies
solid malignancies
TWT-101
TWT101
UHN
University Health Network
Treadwell Therapeutics
Lead sponsor: Treadwell Therapeutics, Inc
Sponsor class: INDUSTRY
Collaborators: name: TIO Discovery Engine
First posted: 2020-08-20
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation and expansion for monotherapy and combination arms with pembrolizumab
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This study will be a first-in-human study evaluating the safety and tolerability of CFI-402411 in subjects with advanced solid malignancies, when CFI-402411 is administered as a single agent or in combination with pembrolizumab. CFI-402411 is an oral pill that blocks the function of HPK1. Blocking HPK1 could stimulate an immune response against the tumor in patients. This immune response could be further enhanced when combined with pembrolizumab. The data obtained from this study will determine the dose and schedule and subject selection for further clinical studies.

Pre-clinical findings support further development of CFI-402411 as a novel anti-cancer agent, and the combination of CFI-402411 with pembrolizumab as a potential strategy to improve outcomes of subjects with advanced malignancies.

Eligibility criteria: 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).

Primary outcomes:
measure: To assess the incidence of adverse events of CFI-402411 as a single agent and at the recommended phase 2 dose (RP2D).
timeFrame: 48 months
measure: To assess the incidence of adverse events with CFI-402411 in combination with pembrolizumab and at the RP2D.
timeFrame: 48 months
measure: To examine best overall response rate in subjects treated at multiple dose levels of CFI-402411.
timeFrame: 48 months
measure: To examine progression free survival in subjects treated at multiple dose levels of CFI-402411.
timeFrame: 48 months
Secondary outcomes:
measure: To identify the maximum tolerated dose of single agent CFI-402411 alone and in combination with pembrolizumab.
timeFrame: 48 months
measure: To further assess the incidence of adverse events of CFI-402411.
timeFrame: 48 months
measure: To assess best overall response of CFI-402411 monotherapy and in combination with pembrolizumab.
timeFrame: 48 months
measure: To assess overall response rates of CFI-402411 monotherapy and in combination with pembrolizumab.
timeFrame: 48 months
measure: To assess overall survival of CFI-402411 monotherapy and in combination with pembrolizumab.
timeFrame: 48 months
measure: To assess progression free survival of CFI-402411 monotherapy and in combination with pembrolizumab.
timeFrame: 48 months
measure: To assess duration of response of CFI-402411 monotherapy and in combination with pembrolizumab.
timeFrame: 48 months
measure: To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through AUC.
timeFrame: 48 months
measure: To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Cmax.
timeFrame: 48 months
measure: To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Tmax.
timeFrame: 48 months
measure: To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab though Cmin.
timeFrame: 48 months
measure: To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through T1/2.
timeFrame: 48 months
measure: To evaluate the effect of CFI-402411 treatment on immune- or disease related biomarkers.
timeFrame: 48 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Grand Rapids
country: United States
facility: START - Mid-West
state: Michigan
city: Nashville
country: United States
facility: SCRI - Nashville
state: Tennessee
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: START - San Antonio
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialist
state: Virginia
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: The Angeles Clinic, Los Angeles
name: Omid Hamid, Dr
role: PRINCIPAL_INVESTIGATOR
References: