Breast CancerPhase 1/2IT-01NCT03058289
A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6
A Phase 1/2 study testing INT230-6, anti-PD-1 antibody and anti-CTLA-4 antibody in people with Breast Cancer and Head and Neck Cancer, run by Intensity Therapeutics, Inc. at 8 sites in 2 countries.
Trial summary
This study evaluated the intratumoral administration of escalating doses of a novel, experimental drug, INT230-6. The study was conducted in patients with several types of refractory cancers including those at the surface of the skin (breast, squamous cell, head and neck) and tumors within the body such (pancreatic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Head and Neck Cancer, Squamous Cell Carcinoma
- What is being tested?
- INT230-6, anti-PD-1 antibody and anti-CTLA-4 antibody
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 9 Feb 2017to 22 Feb 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- INT230-6 monotherapy Cohorts EC2 and EC3, combination with KEYTRUDA® cohort DEC2 and combination with Yervoy cohort FEC. Where criteria diverge the DEC2 and FEC specific criteria will be noted.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Men and Women > 18 years of age on the day of signing consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status < 2; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for ECOG criteria).
- Populations: INT230-6 will be injected into deep or superficial tumors for subjects with histologically or cytologically confirmed advanced or metastatic cancers; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for Populations).
- Includes subjects with loco-regional disease that have relapsed/recurred within 6 months of chemo-radiation and who have no standard of care.
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- Subjects with metastatic disease who have failed one or more approved standard therapies, or have no alternate approved therapy available. Failure of all approved therapies that have a modest or marginal impact on survival is not required as long as the treating physician believes that treatment on study is appropriate for the subject and documents that the subject elects to defer the approved therapies.
- Note: There is no limit on the number of prior therapies that a patient (subject) may have received prior to enrollment in any cohort.
- Subjects must have measurable disease by iRECIST 1.1 criteria including one target tumor for injection by the local site investigator/radiology. Superficial tumors must have one tumor greater than or equal to 1.0 cm, deep tumors greater than or equal to 1.0 cm (as measured by caliper (for non-injected tumors only) or image guidance). Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Subjects must have a minimum of one injectable lesion as determined by the investigator (for superficial tumors) or radiologist (deep tumors).
- Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer: systemic or IT) must have been completed at least 4 weeks prior to dosing (with the exception of kinase inhibitors or other short half-life drugs, a 2 week washout is acceptable prior to treatment) and all adverse events have either returned to baseline or stabilized.
- Note: Subjects who have received prior platinum therapy are eligible irrespective of their response.
- Prior systemic radiation therapy (either IV, intrahepatic or oral) completed at least 4 weeks prior to study drug administration; (for ipilimumab combination please see supplement FEC exclusion criteria).
- Prior focal radiotherapy completed at least 2 weeks prior to study drug administration.
- Prior major treatment-related surgery completed at least 4 weeks prior to study drug administration.
- No prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable as well as off steroid therapy for at least 2 months.
- Life expectancy ≥8 weeks; (for ipilimumab combination please see supplement FEC inclusion criteria).
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
- A WOCBP subject who may become pregnant or who are sexually active with a partner and who could become pregnant agrees to use an effective form of barrier contraception during the study and for at least 180 days in monotherapy; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for pregnancy criteria). (Male subjects must agree to use contraception and refrain from sperm donation during the study for 180 days after administration of study drug.)
- Have adequate organ function as defined by the below screening laboratory values that must meet the following criteria:
- WBC ≥2000/μL (≥2 x 109/L).
- Neutrophils ≥1000/μL (≥1 x 109/L); (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for neutrophil criteria).
- For subjects with planned superficial only injections: PT, PTT/aPTT, and INR ≤1.5 × ULN, Platelets ≥70x103/μL (≥ 70 x 109/L), Hemoglobin ≥8 g/dL
- Creatinine within the institution's laboratory upper limit of normal or calculated creatinine clearance >50 ml/min; (for pembrolizumab combination please see supplements DEC/DEC2 for creatine criteria).
- ALT (SGOT)/AST (SGPT) ≤2.5 x ULN without, and ≤ 5 x ULN with hepatic metastases.
- Bilirubin ≤2 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin <3.0 mg/dL (<52 µmol/L); (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for bilirubin criteria).
- For subjects with planned deep tumor injections: PT, PTT/aPPT, and INR within normal limits; Platelet count ≥100,000/μL; hemoglobin ≥ 9 g/dL.
- Note: ALT (SGPT) =alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT) =aspartate aminotransferase (serum glutamic oxaloacetic transaminase); ULN=upper limit of normal.
- 1 Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
- Additional criteria for combination arms can be found in the appropriate combination protocol supplements. Refer to the Investigative site for details.
- Additional Inclusion Criteria for DEC2 cohort (anti-PD1 combination, KEYTRUDA® (pembrolizumab)) Population: Subjects with histologically or cytologically confirmed advanced or metastatic Pancreatic, Cholangiocarcinoma, non-MSI-H and/or MMR proficient colorectal cancer, and Squamous Cell Carcinoma tumors.
- Additional Inclusion Criteria for FEC cohort (anti-CTLA-4 combination, Yervoy (ipilimumab)) Population: Subjects with histologically or cytologically confirmed advanced or metastatic Hepatocellular carcinoma (HCC), breast cancer regardless of histology (BC) or soft tissue sarcoma
- NOTE: DEC and FEC combination cohorts have additional Inclusion Criteria - refer to the Investigative site for details.
Who cannot join
- For INT230-6 Monotherapy cohort EC3, cohort DEC2-KEYTRUDA® combination and cohort FEC-Yervoy combination
- Subjects who exhibit any of the following conditions at screening will not be eligible for admission into the study:
- History of severe hypersensitivity reactions to cisplatin or vinblastine or other products of the same class.
- Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or superficial bladder cancer, or any other cancer from which the subject has been disease-free for at least 2 years.
- Subjects with tumors >15 cm (in longest diameter). Treatment plan for subjects with tumors that are 9 to15 cm must be discussed with and approved by the medical monitor.
- Underlying medical condition that, in the Principal Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events.
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- Concurrent medical condition requiring the use of immunosuppressive medications, or systemic corticosteroids (topical steroids are permitted); systemic corticosteroids must be discontinued at least 4 weeks prior to dosing. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the subject is on a stable dose. Non-absorbed intra-articular steroid injections will be permitted; or use of other investigational drugs (drugs not marketed for any indication) within 30 days prior to study drug administration. Use of steroids as prophylactic treatment for subjects with contrast allergies to diagnostic imaging contrast dyes will be permitted.
- For deep tumor cohorts, subjects who require uninterrupted anticoagulants of any type, on daily aspirin therapy or NSAIAs.
- Use of other investigational drugs (drugs not marketed for any indication) within 28 days prior to study drug administration.
- Pregnancy Exclusion:
- A WOCBP who has a positive urine pregnancy test (e.g., within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- NOTE: DEC or FEC combination cohorts have additional Exclusion criteria. Refer to the Investigative site for details.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21205
Center for Oncology and Blood Disorders
Houston, Texas, 77030
USC Norris
Los Angeles, California, 90033
Columbia University Medical Center
New York, New York, 10032
USC HOAG
Newport Beach, California, 92663
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
UMASS Memorial Medical Center
Worcester, Massachusetts, 01655
Canada1 site
Princess Margaret Cancer Center - University Health Network
Toronto, Ontario, M5G 1Z5
About this study
Official title: A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects With Advanced Refractory Cancers
This study evaluated the intratumoral administration of escalating doses of a novel, experimental drug, INT230-6. The study was conducted in patients with several types of refractory cancers including those at the surface of the skin (breast, squamous cell, head and neck) and tumors within the body such (pancreatic, colon, liver, lung, etc.). Sponsor also tested INT230-6 in combination with anti-PD-1 and anti-CTLA-4 antibodies.
Read the detailed description
INT230-6 is comprised of 3 agents in a fixed ratio - a cell permeation enhancer and two, potent anti-cancer payloads (cisplatin and vinblastine sulfate). The penetration enhancer facilitates dispersion of the two drugs throughout injected tumors and enables increased diffusion into cancer cells. Nonclinical safety studies showed no findings following drug injection into healthy tissues.
Historically physicians administer the two active drugs comprising INT230-6 by intravenous (IV) infusion to achieve a systemic blood level at the limit of tolerability. The objective is destroy both visible tumors and unseen circulating cancer cells (micro-metastases). Unfortunately, dosing drugs IV delivers only a small amount with a low concentration at the tumor site. This approach especially for late stage cancers is not highly effective and often quite toxic to the patient.
Attempts at direct intratumoral injection with chemotherapeutic agents have not shown the ability to treat the injected tumor, non-injected tumors or micro-metastases. This lack of efficacy for local administration is due possibly to poor dispersion and a lack of cell uptake of the agents.
Due to the use of the novel cell penetration enhancing agent INT230-6 treatment demonstrated strong efficacy in animals having large tumors. The Sponsor's in vivo, non-clinical data shows that INT230-6 thoroughly saturates and kills injected tumors. In addition, the drug induces an adaptive (T-cell mediated) immune response that attacks not only the injected tumor, but non-injected tumors and unseen micro-metastases. Cured animals become permanently immunized against the type of cancer that INT230-6 eliminates.
Clinical trial IT-01 sought to determine the safety and potential efficacy of dosing INT230-6 directly into several different types of cancers. In addition, animal studies showed a strong synergy of INT230-6 with immune modulation agents. Thus, as part of study IT-01 the Sponsor seeks to understand the safety and efficacy of INT230-6 when administered in combination with immuno-therapeutic agents such as antibodies that target Programmed Cell Death (PD-1 or anti-PD-1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4 or anti-CTLA-4) receptors.
This study sought to understand whether tumor regression can be achieved, and patient outcomes improved.
- Conditions
- Breast Cancer, Head and Neck Cancer, Squamous Cell Carcinoma, Lymphoma, Pancreatic Cancer, Liver Cancer
- Being tested
- INT230-6, anti-PD-1 antibody, anti-CTLA-4 antibody
- Keywords
- Neoplasm, Malignancy, Intratumoral, Intralesional, anti-PD-1 antibodies, Immuno therapy, Dose escalation, Platinum, Intensity Therapeutics, INT230-6, Cisplatin, Vinblastine, PD-1, Vinca, KEYTRUDA®, Pembrolizumab, CTLA-4, Carcinoma, Yervoy, Ipilimumab
- Medical subject headings
- Breast Neoplasms, Head and Neck Neoplasms, Carcinoma, Squamous Cell, Lymphoma, Pancreatic Neoplasms, Liver Neoplasms, Colonic Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INT230-6Drug
INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated.
The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.
anti-PD-1 antibodyBiological
Also called pembrolizumab, KEYTRUDA®, MK-3475
The anti-PD-1 antibody will be added concomitantly with INT230-6 as noted in cohort DEC and DEC2
anti-CTLA-4 antibodyBiological
Also called ipilimumab, Yervoy, BMS-734016
The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy With >=40% Total Tumor Burden Dosed (Cohorts A1/B1/EA/EC/EC2/EC3) | Experimental | Dosing: >=40% Total Tumor Burden
A1:INT230-6 injections into only superficial tumors, low starting dose, low concentration per tumor.
B1:INT230-6 injections into deep tumors, low starting dose, low drug concentration per tumor
Dosing schedule for A1 and B1 is every 28 days for 5 sessions
EA:INT230-6 injections into superficial tumors, medium starting dose, low drug concentration per tumor
EC:INT230-6 injections into superficial or deep tumors, moderately high starting dose, high drug concentration per tumor
EC2:INT230-6 injections into superficial or deep tumors, high starting dose, moderate drug concentration per tumor, higher number of tumors to be treated per session than EC.
EC3:INT230-6 injections at fixed maximal dose into superficial or deep tumors, unlimited number of tumors to be treated per session with retreatment once every 9 weeks for two years.
Dosing schedule for EA, EC, EC2 and EC3 is every 2 weeks for 5 sessions
Completed Cohorts Receives: Drug: INT230-6 |
| Monotherapy With <40% Total Tumor Burden Dosed (Cohorts A1/B1/EA/EC/EC2/EC3) | Experimental | Dosing: <40% Total Tumor Burden
A1:INT230-6 injections into only superficial tumors, low starting dose, low concentration per tumor.
B1:INT230-6 injections into deep tumors, low starting dose, low drug concentration per tumor
Dosing schedule for A1 and B1 is every 28 days for 5 sessions
EA:INT230-6 injections into superficial tumors, medium starting dose, low drug concentration per tumor
EC:INT230-6 injections into superficial or deep tumors, moderately high starting dose, high drug concentration per tumor
EC2:INT230-6 injections into superficial or deep tumors, high starting dose, moderate drug concentration per tumor, higher number of tumors to be treated per session than EC.
EC3:INT230-6 injections at fixed maximal dose into superficial or deep tumors, unlimited number of tumors to be treated per session with retreatment once every 9 weeks for two years.
Dosing schedule for EA, EC, EC2 and EC3 is every 2 weeks for 5 sessions
Completed Cohorts Receives: Drug: INT230-6 |
| INT230-6 Combined With Pembrolizumab (Cohorts DEC/DEC2) | Experimental | DEC: INT230-6 injections every 2 weeks for 5 sessions with the possibility for INT230-6 retreatment into superficial tumors, with addition of anti-PD-1 antibody KEYTRUDA® (pembrolizumab) dosed concurrently starting at Day 1 every 3 weeks for two years for selected cancer types.
Completed Cohort
DEC2:INT230-6 per the dosing of cohort EC3 combined with KEYTRUDA® (pembrolizumab) dosed per DEC concurrently starting at Day 1 for selected cancers.
Completed Cohort Receives: Drug: INT230-6; Biological: anti-PD-1 antibody |
| INT 230-6 Combined With Ipilimumab (Cohort FEC) | Experimental | FEC: INT230-6 per the EC3 regimen combined with Yervoy (ipilimumab) dosed concurrently starting at Day 1 every 3 weeks for four treatments for selected cancer types.
Completed Cohort anti-CTLA-4 antibody: The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC. Receives: Drug: INT230-6; Biological: anti-CTLA-4 antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5)
The primary objective is to assess the safety and tolerability of single and multiple intratumoral doses of INT230-6 in subjects with advanced or recurrent malignancies. This will be assessed by the rate of ≥ grade 3 AE's attributed to INT230-6 and not the underlying disease.
NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 (least severe) to 5 (most severe))
All recorded adverse events will be listed and tabulated by system organ class, preferred term, and dose and coded according to the most current version of MedDRA. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance.
Adverse Events will be summarized for all reported data and by study period: a) up to and including 28 days post last dose of initial treatment, and b) from first dose of re-initiation of treatment, for subjects who re-initiate study therapy while in follow-up, up to 28 days post-dose of the last re-treatment dose.
Measured: Up to 5 years
Secondary outcomes (4)
Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria,
Assess the preliminary efficacy of INT230-6 by measuring the disease control rate (CR+PR+SD) as assessed by iRECIST. Complete response (CR) and partial response (PR) will be defined for injected tumors followed per RECIST 1.1 utilizing target lesions. Progressive disease will be determined by clinical or radiological deterioration leading to the subject being taken off-treatment at the discretion of the investigator. Stable disease (SD) is defined as any adequate assessment not considered CR, PR, or progression.
Measured: Up to 5 years
Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6.
Characterize the peak plasma profile for the three INT230-6 components after single and then multiple IT tumor site injections for safety purposes.
Timepoints for sample collection were T = 1 Hours after dosing.
Mean dose volume categories that were used to summarize data were as follows:
2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range >6 to 12 mL) 17 mL (range >12 to 24 mL) 30 mL (range >24 mL to 44 mL) 68 mL (range >44 to 98 mL) 118 mL (range >98 to 175 mL)
Measured: T = 1 hour after first dose
Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6.
Characterize the pharmacokinetic AUC profile of each of the three INT230-6 components for AUC after single IT tumor site injection for safety purposes.
Timepoints for sample collection were T = 0, 1, 3, 6, 24 Hours after dosing.
Mean dose volume categories that were used to summarize data were as follows:
2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range >6 to 12 mL) 17 mL (range >12 to 24 mL) 30 mL (range >24 mL to 44 mL) 68 mL (range >44 to 98 mL) 118 mL (range >98 to 175 mL)
Measured: T= 0, 1, 3, 6, 24 Hours after dosing
Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6.
Characterize the half life of each of the three INT230-6 components after single and multiple IT tumor site injections for safety purposes.
Timepoints for sample collection were T = 0, 1, 3, 6, 24 Hours after dosing.
Mean dose volume categories that were used to summarize data were as follows:
2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range >6 to 12 mL) 17 mL (range >12 to 24 mL) 30 mL (range >24 mL to 44 mL) 68 mL (range >44 to 98 mL) 118 mL (range >98 to 175 mL)
Measured: T= 0, 1, 3, 6, 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2017
- Study start9 Feb 2017
- Primary completion22 Feb 2023
- Study completion22 Feb 2023
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.
- Other trials for Breast CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- There were 6 cohorts in the escalation portion of the protocol. Five dosed INT230-6 alone and one was combined with pembrolizumab. Cohorts A and B1 treated superficial tumors at a 1:4 ratio of drug to tumor with a low tumor load once per month. Cohort EA was similar to cohort A with INT230-6 every 2 weeks. Cohort EC escalated the total and maximal dose per any one tumor to a ratio of 1:2 \& dosed every two weeks. Cohort EC2 explored a drug load ratio of 1:3 and escalated the dose per tumor further. Cohort DEC combined INT230-6 with a fixed amount of pembrolizumab. Completed, non-escalation cohorts include 1) monotherapy INT230-6 cohort (EC3) dosed every two weeks 2) INT230-6 in a combination with pembrolizumab (DEC2) and 3) INT230-6 in combination with ipilimumab (FEC). Other specific regimens or combinations of INT230-6 may be designated by the Study Steering Committee.
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intensity Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Brian Schwartz, M.D., Study director, Intensity TherapeuticsLillian Siu, M.D., FRCP, Study chair, Princess Margaret Hospital, CanadaAnthony El-Khoueiry, M.D., Principal investigator, USC Norris and HOAG sitesAnthony J. Olszanski, M.D., RPh, Principal investigator, Fox Chase Cancer CenterNilofer Azad, M.D., Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsGiles F Whalen, M.D., Principal investigator, UMASS Memorial Medical GroupMatthew Ingham, M.D., Principal investigator, Columbia UniversityLuis Camacho, M.D., Principal investigator, Center for Oncology and Blood Disorders
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03058289
- Sponsor's protocol ID
- IT-01
- Other IDs
- KEYNOTE KN-A10, CA184-592
- Acronym
- IT-01
- Status last verified
- May 2024
- First submitted
- 10 Feb 2017
- Last updated
- 27 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects With Advanced Refractory Cancers
- ClinicalTrials.gov ID
- NCT03058289
- Acronym / sponsor ID
- IT-01 / IT-01
- Conditions
- Breast Cancer, Head and Neck Cancer, Squamous Cell Carcinoma, Lymphoma, Pancreatic Cancer, Liver Cancer
- Keywords
- Neoplasm, Malignancy, Intratumoral, Intralesional, anti-PD-1 antibodies, Immuno therapy, Dose escalation, Platinum
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- Intensity Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC, Bristol-Myers Squibb
- Study start
- 9 Feb 2017 (actual)
- Primary completion
- 22 Feb 2023 (actual)
- Study completion
- 22 Feb 2023 (actual)
- First posted
- 20 Feb 2017 (actual)
- Results
- Posted 13 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated the intratumoral administration of escalating doses of a novel, experimental drug, INT230-6. The study was conducted in patients with several types of refractory cancers including those at the surface of the skin (breast, squamous cell, head and neck) and tumors within the body such (pancreatic, colon, liver, lung, etc.). Sponsor also tested INT230-6 in combination with anti-PD-1 and anti-CTLA-4 antibodies.
Detailed description
INT230-6 is comprised of 3 agents in a fixed ratio - a cell permeation enhancer and two, potent anti-cancer payloads (cisplatin and vinblastine sulfate). The penetration enhancer facilitates dispersion of the two drugs throughout injected tumors and enables increased diffusion into cancer cells. Nonclinical safety studies showed no findings following drug injection into healthy tissues.
Historically physicians administer the two active drugs comprising INT230-6 by intravenous (IV) infusion to achieve a systemic blood level at the limit of tolerability. The objective is destroy both visible tumors and unseen circulating cancer cells (micro-metastases). Unfortunately, dosing drugs IV delivers only a small amount with a low concentration at the tumor site. This approach especially for late stage cancers is not highly effective and often quite toxic to the patient.
Attempts at direct intratumoral injection with chemotherapeutic agents have not shown the ability to treat the injected tumor, non-injected tumors or micro-metastases. This lack of efficacy for local administration is due possibly to poor dispersion and a lack of cell uptake of the agents.
Due to the use of the novel cell penetration enhancing agent INT230-6 treatment demonstrated strong efficacy in animals having large tumors. The Sponsor's in vivo, non-clinical data shows that INT230-6 thoroughly saturates and kills injected tumors. In addition, the drug induces an adaptive (T-cell mediated) immune response that attacks not only the injected tumor, but non-injected tumors and unseen micro-metastases. Cured animals become permanently immunized against the type of cancer that INT230-6 eliminates.
Clinical trial IT-01 sought to determine the safety and potential efficacy of dosing INT230-6 directly into several different types of cancers. In addition, animal studies showed a strong synergy of INT230-6 with immune modulation agents. Thus, as part of study IT-01 the Sponsor seeks to understand the safety and efficacy of INT230-6 when administered in combination with immuno-therapeutic agents such as antibodies that target Programmed Cell Death (PD-1 or anti-PD-1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4 or anti-CTLA-4) receptors.
This study sought to understand whether tumor regression can be achieved, and patient outcomes improved.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- There were 6 cohorts in the escalation portion of the protocol. Five dosed INT230-6 alone and one was combined with pembrolizumab. Cohorts A and B1 treated superficial tumors at a 1:4 ratio of drug to tumor with a low tumor load once per month. Cohort EA was similar to cohort A with INT230-6 every 2 weeks. Cohort EC escalated the total and maximal dose per any one tumor to a ratio of 1:2 \& dosed every two weeks. Cohort EC2 explored a drug load ratio of 1:3 and escalated the dose per tumor further. Cohort DEC combined INT230-6 with a fixed amount of pembrolizumab. Completed, non-escalation cohorts include 1) monotherapy INT230-6 cohort (EC3) dosed every two weeks 2) INT230-6 in a combination with pembrolizumab (DEC2) and 3) INT230-6 in combination with ipilimumab (FEC). Other specific regimens or combinations of INT230-6 may be designated by the Study Steering Committee.
| Arm | Type | Receives |
|---|---|---|
| Monotherapy With >=40% Total Tumor Burden Dosed (Cohorts A1/B1/EA/EC/EC2/EC3) | Experimental | Drug: INT230-6Dosing: >=40% Total Tumor Burden A1:INT230-6 injections into only superficial tumors, low starting dose, low concentration per tumor. B1:INT230-6 injections into deep tumors, low starting dose, low drug concentration per tumor Dosing schedule for A1 and B1 is every 28 days for 5 sessions EA:INT230-6 injections into superficial tumors, medium starting dose, low drug concentration per tumor EC:INT230-6 injections into superficial or deep tumors, moderately high starting dose, high drug concentration per tumor EC2:INT230-6 injections into superficial or deep tumors, high starting dose, moderate drug concentration per tumor, higher number of tumors to be treated per session than EC. EC3:INT230-6 injections at fixed maximal dose into superficial or deep tumors, unlimited number of tumors to be treated per session with retreatment once every 9 weeks for two years. Dosing schedule for EA, EC, EC2 and EC3 is every 2 weeks for 5 sessions Completed Cohorts |
| Monotherapy With <40% Total Tumor Burden Dosed (Cohorts A1/B1/EA/EC/EC2/EC3) | Experimental | Drug: INT230-6Dosing: <40% Total Tumor Burden A1:INT230-6 injections into only superficial tumors, low starting dose, low concentration per tumor. B1:INT230-6 injections into deep tumors, low starting dose, low drug concentration per tumor Dosing schedule for A1 and B1 is every 28 days for 5 sessions EA:INT230-6 injections into superficial tumors, medium starting dose, low drug concentration per tumor EC:INT230-6 injections into superficial or deep tumors, moderately high starting dose, high drug concentration per tumor EC2:INT230-6 injections into superficial or deep tumors, high starting dose, moderate drug concentration per tumor, higher number of tumors to be treated per session than EC. EC3:INT230-6 injections at fixed maximal dose into superficial or deep tumors, unlimited number of tumors to be treated per session with retreatment once every 9 weeks for two years. Dosing schedule for EA, EC, EC2 and EC3 is every 2 weeks for 5 sessions Completed Cohorts |
| INT230-6 Combined With Pembrolizumab (Cohorts DEC/DEC2) | Experimental | Drug: INT230-6, Biological: anti-PD-1 antibodyDEC: INT230-6 injections every 2 weeks for 5 sessions with the possibility for INT230-6 retreatment into superficial tumors, with addition of anti-PD-1 antibody KEYTRUDA® (pembrolizumab) dosed concurrently starting at Day 1 every 3 weeks for two years for selected cancer types. Completed Cohort DEC2:INT230-6 per the dosing of cohort EC3 combined with KEYTRUDA® (pembrolizumab) dosed per DEC concurrently starting at Day 1 for selected cancers. Completed Cohort |
| INT 230-6 Combined With Ipilimumab (Cohort FEC) | Experimental | Drug: INT230-6, Biological: anti-CTLA-4 antibodyFEC: INT230-6 per the EC3 regimen combined with Yervoy (ipilimumab) dosed concurrently starting at Day 1 every 3 weeks for four treatments for selected cancer types. Completed Cohort anti-CTLA-4 antibody: The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- INT230-6 monotherapy Cohorts EC2 and EC3, combination with KEYTRUDA® cohort DEC2 and combination with Yervoy cohort FEC. Where criteria diverge the DEC2 and FEC specific criteria will be noted.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Men and Women > 18 years of age on the day of signing consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status < 2; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for ECOG criteria).
- Populations: INT230-6 will be injected into deep or superficial tumors for subjects with histologically or cytologically confirmed advanced or metastatic cancers; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for Populations).
Key exclusion criteria (12 listed)
- For INT230-6 Monotherapy cohort EC3, cohort DEC2-KEYTRUDA® combination and cohort FEC-Yervoy combination
- Subjects who exhibit any of the following conditions at screening will not be eligible for admission into the study:
- History of severe hypersensitivity reactions to cisplatin or vinblastine or other products of the same class.
- Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or superficial bladder cancer, or any other cancer from which the subject has been disease-free for at least 2 years.
- Subjects with tumors >15 cm (in longest diameter). Treatment plan for subjects with tumors that are 9 to15 cm must be discussed with and approved by the medical monitor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INT230-6INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated. The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations. | Drug | INT 230-6 Combined With Ipilimumab (Cohort FEC), INT230-6 Combined With Pembrolizumab (Cohorts DEC/DEC2), Monotherapy With <40% Total Tumor Burden Dosed (Cohorts A1/B1/EA/EC/EC2/EC3), Monotherapy With >=40% Total Tumor Burden Dosed (Cohorts A1/B1/EA/EC/EC2/EC3) |
| anti-PD-1 antibodyAlso: pembrolizumab, KEYTRUDA®, MK-3475The anti-PD-1 antibody will be added concomitantly with INT230-6 as noted in cohort DEC and DEC2 | Biological | INT230-6 Combined With Pembrolizumab (Cohorts DEC/DEC2) |
| anti-CTLA-4 antibodyAlso: ipilimumab, Yervoy, BMS-734016The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC | Biological | INT 230-6 Combined With Ipilimumab (Cohort FEC) |
Primary outcome
Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5)
Time frame: Up to 5 years
The primary objective is to assess the safety and tolerability of single and multiple intratumoral doses of INT230-6 in subjects with advanced or recurrent malignancies. This will be assessed by the rate of ≥ grade 3 AE's attributed to INT230-6 and not the underlying disease. NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 (least severe) to 5 (most severe)) All recorded adverse events will be listed and tabulated by system organ class, preferred term, and dose and coded according to the most current version of MedDRA. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance. Adverse Events will be summarized for all reported data and by study period: a) up to and including 28 days post last dose of initial treatment, and b) from first dose of re-initiation of treatment, for subjects who re-initiate study therapy while in follow-up, up to 28 days post-dose of the last re-treatment dose.
4 secondary outcomes
Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria,
Time frame: Up to 5 years
Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6.
Time frame: T = 1 hour after first dose
Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6.
Time frame: T= 0, 1, 3, 6, 24 Hours after dosing
Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6.
Time frame: T= 0, 1, 3, 6, 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Schwartz, M.D. study director
Intensity Therapeutics
Lillian Siu, M.D., FRCP study chair
Princess Margaret Hospital, Canada
Anthony El-Khoueiry, M.D. principal investigator
USC Norris and HOAG sites
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing INT230-6, anti-PD-1 antibody and anti-CTLA-4 antibody in people with Breast Cancer and Head and Neck Cancer, run by Intensity Therapeutics, Inc. at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.