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A Phase 1/2 Safety Study of Intratumorally Dosed INT230-6

Study Purpose

This study evaluates the intratumoral administration of escalating doses of a novel, experimental drug, INT230-6. The study is being 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 plans to test INT230-6 in combination with anti-PD-1 and anti-CTLA-4 antibodies.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

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. 1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 2. Men and Women > 18 years of age on the day of signing consent. 3. 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). 4. 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). 5. Includes subjects with loco-regional disease that have relapsed/recurred within 6 months of chemo-radiation and who have no standard of care. 6. 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. 7. 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. 8. Subjects must have a minimum of one injectable lesion as determined by the investigator (for superficial tumors) or radiologist (deep tumors). 9. 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. 10. 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). 11. Prior focal radiotherapy completed at least 2 weeks prior to study drug administration. 12. Prior major treatment-related surgery completed at least 4 weeks prior to study drug administration. 13. 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. 14. Life expectancy ≥8 weeks; (for ipilimumab combination please see supplement FEC inclusion criteria). 15. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) 2. 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.) 16. Have adequate organ function as defined by the below screening laboratory values that must meet the following criteria: 1. WBC ≥2000/μL (≥2 x 109/L). 2. Neutrophils ≥1000/μL (≥1 x 109/L); (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for neutrophil criteria). 3. 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. 4. 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). 5. ALT (SGOT)/AST (SGPT) ≤2.5 x ULN without, and ≤ 5 x ULN with hepatic metastases. 6. 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). 7. 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. 17. 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.

Exclusion Criteria:

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: 18. History of severe hypersensitivity reactions to cisplatin or vinblastine or other products of the same class. 19. 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. 20. 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. 21. 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. 22. 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. 23. For deep tumor cohorts, subjects who require uninterrupted anticoagulants of any type, on daily aspirin therapy or NSAIAs. 24. 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03058289
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Intensity Therapeutics, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Ian B. Walters, M.D.Lillian Siu, M.D., FRCPAnthony El-Khoueiry, M.D.Anthony J. Olszanski, M.D., RPhNilofer Azad, M.D.Giles F Whalen, M.D.Matthew Ingham, M.D.Luis Camacho, M.D.
Principal Investigator Affiliation Intensity TherapeuticsPrincess Margaret Hospital, CanadaUSC Norris and HOAG sitesFox Chase Cancer CenterSidney Kimmel Comprehensive Cancer Center at Johns HopkinsUMASS Memorial Medical GroupColumbia UniversityCenter for Oncology and Blood Disorders
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Canada, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Breast Cancer, Head and Neck Cancer, Squamous Cell Carcinoma, Lymphoma, Pancreatic Cancer, Liver Cancer, Colon Cancer, Lung Cancer, Bile Duct Cancer, Chordoma of Sacrum, Sarcoma
Additional Details

INT230-6 is comprised of a 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 demonstrates 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 seeks 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 seeks to understand whether tumor regression can be achieved and patient outcomes improved.

Arms & Interventions

Arms

Experimental: Cohort A

INT230-6 injections every 28 days for 5 sessions into only superficial tumors, low starting dose, low concentration per tumor. Closed to enrollment

Experimental: Cohort B1

INT230-6 injections every 28 days for 5 sessions into deep tumors, low starting dose, low drug concentration per tumor Closed to enrollment

Experimental: Cohort EA

INT230-6 injections every 2 weeks for 5 sessions into superficial tumors, medium starting dose, low drug concentration per tumor Closed to enrollment

Experimental: Cohort EC

INT230-6 injections every 2 weeks for 5 sessions into superficial or deep tumors, moderately high starting dose, high drug concentration per tumor Closed to enrollment

Experimental: Cohort EC2

INT230-6 injections every 2 weeks for 5 sessions into superficial or deep tumors, high starting dose, moderate drug concentration per tumor, higher number of tumors to be treated per session than EC

Experimental: Cohort DEC: Safety with INT230-6

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. Closed to enrollment

Experimental: EC3: INT230-6 monotherapy fixed maximal dose

INT230-6 injections every 2 weeks for 5 sessions 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.

Experimental: DEC2: INT230-6 combined with pembrolizumab

INT230-6 per the dosing of cohort EC3 combined with Keytruda (pembrolizumab) dosed per DEC concurrently starting at Day 1 for selected cancers.

Experimental: FEC: INT230-6 combined with ipilimumab

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.

Interventions

Drug: - INT230-6

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. The drug is stored frozen and must be dosed at room temperature. The drug dose to be administered is set by the tumor volume of the target lesions - not the subject's body surface area

Biological: - anti-PD-1 antibody

The anti-PD-1 antibody will be added concomitantly with INT230-6 as noted in cohort DEC and DEC2

Biological: - anti-CTLA-4 antibody

The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

USC Norris, Los Angeles, California

Status

Recruiting

Address

USC Norris

Los Angeles, California, 90033

Site Contact

Xiomara Menendez

xiomara.menendez@med.usc.edu

323-409-4368

USC HOAG, Newport Beach, California

Status

Recruiting

Address

USC HOAG

Newport Beach, California, 92663

Site Contact

Cristina de Leon

cristina.deleon@hoag.org

949-764-5543

Baltimore, Maryland

Status

Recruiting

Address

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21205

Site Contact

Jennifer Hale, RN

phase1trials@exchange.johnshopkins.edu

410-502-5140

UMASS Memorial Medical Center, Worcester, Massachusetts

Status

Recruiting

Address

UMASS Memorial Medical Center

Worcester, Massachusetts, 01655

Site Contact

Cancer Research Office

cancer.research@umassmed.edu

508-856-3216

Columbia University Medical Center, New York, New York

Status

Recruiting

Address

Columbia University Medical Center

New York, New York, 10032

Fox Chase Cancer Center, Philadelphia, Pennsylvania

Status

Recruiting

Address

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497

Site Contact

Ikenna Opurum

Ikenna.Opurum@fccc.edu

215-728-5518

Center for Oncology and Blood Disorders, Houston, Texas

Status

Recruiting

Address

Center for Oncology and Blood Disorders

Houston, Texas, 77030

Site Contact

Johnathan Ojo

jojo@clinvax.com

833-254-6829

International Sites

Toronto, Ontario, Canada

Status

Recruiting

Address

Princess Margaret Cancer Center - University Health Network

Toronto, Ontario, M5G 1Z5

Site Contact

Oncology Referral

sirby@catalystcr.com

416-946-4575