Locally Advanced Solid TumorPhase 1NCT03881488
Study of CTX-471 as a Monotherapy or in Combination With Pembrolizumab in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies
A Phase 1 study testing CTX-471 and Pembrolizumab (KEYTRUDA®) in people with Locally Advanced Solid Tumor and Metastatic Cancer, run by Compass Therapeutics at 10 sites in United States.
Trial summary
This is a Phase 1, open-label, first-in-human study of CTX-471 administered as a monotherapy or in combination with pembrolizumab in patients with metastatic or locally advanced malignancies that have progressed while receiving an approved PD-1 or PD-L1 inhibitor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Solid Tumor, Metastatic Cancer, Non-small Cell Lung Cancer
- What is being tested?
- CTX-471 and Pembrolizumab (KEYTRUDA®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 10 sitesUnited States
- Study dates
- 17 May 2019to 21 May 2025
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Histologically confirmed diagnosis:
- Monotherapy Arm 1 ( Part 1 and 2): metastatic or locally advanced malignancies
- Combination Arm 2 Par 1 Dose Escalation: metastatic or locally advanced non-small cell lung, small cell lung cancer, mesothelioma, melanoma, or head and neck cancer
- Combination Arm 2 Part 2 Dose Expansion: metastatic or locally advanced non-small cell lung, small cell lung cancer, or melanoma
- Measurable disease per RECIST 1.1
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- Disease progression after at least 12 weeks and at least 2 doses of a commercially available PD-1 or PD-L1 inhibitor per approved prescriber's information, whether monotherapy or in combination therapy, with no other intervening systemic anticancer therapy prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Life expectancy > 12 weeks
- Adequate bone marrow function defined by ANC of ≥ 1.5×10^9/L, platelet count of ≥100.0×10^9/L, and hemoglobin of ≥ 9.0 g/dL (with or without transfusion)
- For Combination Arm 2: these criteria must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Patients can be on a stable dose of erythropoietin (≥ approximately 3 months)
- Adequate hepatic function defined as serum total bilirubin < 1.5 ULN, AST/ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases)
- Adequate renal function defined as creatinine clearance > 30 mL/min as determined by the Cockcroft-Gault equation
- Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be least 2 years postmenopausal or commits to use 2 acceptable forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment
- Female patients who are women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening within 7 days of dosing with CTX-471 for Monotherapy Arm 1, and within 72 hours of dosing with CTX-471 and pembrolizumab for Combination Arm 2
- For Monotherapy Arm 1 Only: Last dose of previous PD-1 or PD-L1 therapy ≥ 28 days, other anticancer therapy > 21 days (or 2 half-lives for proteins, whichever is longer), radiotherapy > 21 days (concurrent localized palliative radiotherapy is allowed during CTX-471 treatment), or surgical intervention >21 days prior to the first dose of CTX-471
- Resolution of all prior anti-cancer therapy toxicities ≤ Grade 1. Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy may be eligible. Patients with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
- For Monotherapy Arm 1 Only: Willingness to provide pre- and post-treatment fresh tumor biopsies
- Capable of understanding and complying with protocol requirements
- Signed and dated institutional review board/independent ethics committee-approved informed consent form before any protocol-directed screening procedures are performed
Who cannot join
- Developed clinically significant adverse reaction to PD-1 or PD-L1 therapy, including immune related adverse reactions, which led to discontinuation of treatment
- Prior treatment with other investigational immune-oncology therapies
- Systemic therapy with immunosuppressive agents within 7 days before the start of CTX-471 treatment. Topical, intranasal, intraocular, or inhaled corticosteroids and physiologic replacement for patients with adrenal insufficiency are allowed
- Patient is a pregnant or lactating WCBP
- Prior solid organ transplantation
- Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus infection (HIV) or a positive serological test at Screening within 28 days of dosing with CTX 471
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- Participants who are HBsAg (hepatitis B surface antigen) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention
- Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
- HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
- Participants on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening
- Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
- Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1)
- Active autoimmune disease or medical conditions requiring chronic steroid (ie, > 10 mg/day prednisone or equivalent) or immunosuppressive therapy. Patients with a prior history of autoimmune disease may be eligible following discussion with the Medical Monitor
- For Monotherapy Arm 1 Only: History of central nervous system metastases
- History of seizure disorders
- Congestive heart failure (> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or clinically significant cardiac arrhythmias
- Other systemic conditions or organ abnormalities that in the opinion of the Investigator may interfere with the conduct and/or interpretation of the current study
- For Combination Arm 2 Only: Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone replacement may be eligible Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention
- For Combination Arm 2 Only: Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease
- For Combination Arm 2 Only: Has had an allogeneic tissue transplant
- For Combination Arm 2 Only: Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Administration of killed vaccines are allowed
- For Combination Arm 2 Only: Has a known additional malignancy that is progressing or has required active treatment within the past 3 years Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of bladder, that have undergone potentially curative therapy are not excluded
- For Combination Arm 2 Only: Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
- For Combination Arm 2 Only: Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
- For Combination Arm 2 Only: Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
- For Combination Arm 2 Only: Has an active infection requiring systemic therapy
- For Combination Arm 2 Only: Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
- For Combination Arm 2 Only: Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
- For Combination Arm 2 Only: Has received radiation therapy to the lung that is > 30Gy within 6 months of the first dose of trial treatment
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Mary Crowley Cancer Research
Dallas, Texas, 75251
Duke University School of Medicine
Durham, North Carolina, 27705
Institute for Translational Oncology Research (ITOR)
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Mt Sinai
New York, New York, 10029
Ocala Oncology Center
Ocala, Florida, 34474
Hematology Oncology Associates Of The Treasure Coast
Port Saint Lucie, Florida, 34952
Washington University School of Medicine, Siteman Cancer Center
St Louis, Missouri, 63110
About this study
Official title: A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of CTX-471 Administered Either as a Monotherapy or in Combination With Pembrolizumab in Patients With Inadequate Responses to PD-1/PD-L1 Checkpoint Inhibitors in Metastatic or Locally Advanced Malignancies
This is a Phase 1, open-label, first-in-human study of CTX-471 administered as a monotherapy or in combination with pembrolizumab in patients with metastatic or locally advanced malignancies that have progressed while receiving an approved PD-1 or PD-L1 inhibitor. The study will be conducted in 2 treatment arms (Monotherapy Arm 1 and Combination Arm 2). Each arm will have two parts: Part 1 Dose Escalation and Part 2 Dose Expansion. In each arm (monotherapy and combination therapy), data from Part 1 (dose escalation) and Part 2 (dose expansion) were combined by dose level for reporting.
- Conditions
- Locally Advanced Solid Tumor, Metastatic Cancer, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Mesothelioma, Melanoma
- Being tested
- CTX-471, Pembrolizumab (KEYTRUDA®)
- Medical subject headings
- Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Mesothelioma, Melanoma, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTX-471Drug
IV infusion every 2 weeks
Pembrolizumab (KEYTRUDA®)Drug
Also called KEYTRUDA®
IV infusion every 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Part 1 Dose Escalation | Experimental | Escalating doses of CTX-471 depending on cohort at enrollment Receives: Drug: CTX-471 |
| Arm 1 Part 2 Dose Expansion | Experimental | Two dose groups of CTX-471 (0.3 mg/kg and 0.6 mg/kg) Receives: Drug: CTX-471 |
| Arm 2 Part 1 Dose Escalation | Experimental | Escalating doses of CTX-471 in combination with pembrolizumab (KEYTRUDA® ) depending on cohort at enrollment Receives: Drug: CTX-471; Drug: Pembrolizumab (KEYTRUDA®) |
| Arm 2 Part 2 Dose Expansion | Experimental | Two cohorts of CTX-471 (0.3 mg/kg and 0.6 mg/kg) in combination with pembrolizumab (KEYTRUDA® ) (400 mg) in three tumor type subgroups. Cohort 1 - Group 1A - NSCLC , Group 1B -SCLC and Group 1C - Melanoma. Cohort 2 Group 2A - NSCLC, Group 2B - SCLC and Group 2C -Melanoma. Receives: Drug: CTX-471; Drug: Pembrolizumab (KEYTRUDA®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs), Treatment-emergent Adverse Events (TEAEs), and/or Changes in Clinical Laboratory Abnormalities
Hematological and nonhematological DLTs were defined in the protocol. TEAE is an occurrence of an adverse event that started or worsened in severity on or after the first dose of CTX-471. Change in clinical laboratory abnormalities is defined as a TEAE related to laboratory results.
Measured: From first CTX-471 dose to 4 weeks after first dose for DLTs in monotherapy arms, to 6 weeks after first dose for DLTs in combination arms, to 60 days after last dose for TEAEs and clinical laboratory abnormalities in both monotherapy and combination arms
Secondary outcomes (8)
Maximum Serum Concentration (Cmax) of CTX-471
Calculated from plasma concentrations measured from samples collected at times shown below
Measured: Monotherapy arms: before Week 1 dose; 1, 6, 24 hours and 2 weeks after Week 1 dose; before Week 9 dose; 1, 6, 24 hours and 2 weeks after Week 9 dose. Combination therapy arms: before Week 1 dose; 1, 6, 24 hours and 2 weeks after Week 1 dose.
Area Under the Serum Concentrations of CTX-471 Versus Time Curve (AUC)
AUC(0-24) = AUC from time 0 to 24 hours (1 day); AUC(0-336) = AUC from time 0 to 336 hours (14 days). Calculated from plasma concentrations measured from samples collected at the time points below.
Measured: Monotherapy arms: before Week 1 dose; 1, 6, 24 hours and 2 weeks after Week 1 dose; before Week 9 dose; 1, 6, 24 hours after Week 9 dose. Combination therapy arms: before Week 1 dose; 1, 6, 24 hours and 2 weeks after Week 1 dose.
Half-life (t1/2) of Serum Concentration of CTX-471
Measured: Calculated from plasma concentrations measured from samples collected before the first dose of CTX-471; 1, 6, and 24 hours after the first dose of CTX-471; and before the second dose of CTX-471 (Weeks 1 to 3)
Development of Anti-drug Antibodies
Frequency of patients with a negative test result for antibody to CTX-471 prior to treatment who had a positive test for antibody to CTX-471 after treatment.
For monotherapy arms, end of treatment was an average 18 weeks, and 60 days after end of treatment was an average 27 weeks. For combination arms, end of treatment was an average 15 weeks, and 60 days after end of treatment was an average 24 weeks.
Measured: Monotherapy arms: Weeks 3, 5, 9, 13, 17, 21, 25, 29, 33, and 37 and end of treatment and 60 days after end of treatment; Combination therapy arms: Weeks 5, 9, 13, 19, 25, 31, and 37 and end of treatment and 60 days after end of treatment
Overall Response Rate
Percentage of patients whose best overall response to treatment was complete response or partial response (as assessed by Response Evaluation Criteria in Solid Tumours guideline version 1.1)
Measured: From the first dose of CTX-471 to treatment discontinuation (average of 18 weeks for monotherapy groups and and average of 15 weeks for combination groups)
Duration of Response
Time period from date of CT or MRI that first confirmed complete or partial response to date of CT or MRI that first confirmed progression of disease (as assessed by Response Evaluation Criteria in Solid Tumours guideline version 1.1)
Measured: From first date of complete or partial response to first date of disease progression or death
Progression-free Survival
Time from the first dose of CTX-471 to disease progression (as assessed by Response Evaluation Criteria in Solid Tumours guideline version 1.1) or death
Measured: From the first dose of CTX-471 to progression of disease or death
Overall Survival
Time from the first dose of CTX-471 to death
Measured: From the first dose of CTX-471 to death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study start17 May 2019
- Primary completion21 May 2025
- Study completion21 May 2025
Why it stopped: The combination therapy arm of the study with pembrolizumab did not yield an efficacy signal, so enrollment into the combination therapy arm was terminated. The monotherapy arm of the study was fully enrolled and completed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Compass Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd, Merck, Sharp & Dohme, LLC, Rahway, NJ USA
- Responsible party
- Sponsor
- Investigators
- Thomas Scheutz, MD, PhD, Study director, Compass Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03881488
- Sponsor's protocol ID
- CTX-471-001
- Other IDs
- KEYNOTE-E65, MK-3475-E65
- Status last verified
- Jun 2025
- First submitted
- 13 Mar 2019
- Last updated
- 9 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Singh R, Kim YH, Lee SJ, Eom HS, Choi BK. 4-1BB immunotherapy: advances and hurdles. Exp Mol Med. 2024 Feb;56(1):32-39. doi: 10.1038/s12276-023-01136-4. Epub 2024 Jan 4.
PubMed 38172595