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

NCT03058289 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: IT-01KEYNOTE KN-A10CA184-592
• Study Type: interventional
• Target: 111
• Locations: 2 countries
• Sites: 8

Brief 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, colon, liver, lung, etc.). Sponsor also tested INT230-6 in combination with anti-PD-1 and anti-CTLA-4 antibodies.

Conditions

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

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; Keynote A10; CA184-592

Outcome Measures

Primary Outcomes (1)

• 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.

  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,

  Up to 5 years

• Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6.

  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.

  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.

  T= 0, 1, 3, 6, 24 hours

Other Outcomes (3)

• Exploratory: Control or Regression of Non Injected Tumors by Measurement of Length (in Centimeters) Radio-graphically Using Computer Tomography or Magnetic Resonance Imaging.

  Up to 18 months

• Exploratory: Blood, Genetic and Tissue Biomarker Identification From Cell Flow Phenotyping, Tissue Analysis, Genetic SNP Analysis.

  Up to 2 months

• Exploratory: Overall Subject Outcome

  Up to 3 years

Study Arms (4)

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

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

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

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.

Drug: INT230-6; Biological: anti-CTLA-4 antibody

Interventions

INT230-6 DRUG

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.

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 antibody BIOLOGICAL

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

Also known as: pembrolizumab, KEYTRUDA®, MK-3475

INT230-6 Combined With Pembrolizumab (Cohorts DEC/DEC2)

anti-CTLA-4 antibody BIOLOGICAL

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

Also known as: ipilimumab, Yervoy, BMS-734016

INT 230-6 Combined With Ipilimumab (Cohort FEC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Intensity Therapeutics, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (8)

USC Norris

Los Angeles, California, 90033, United States

Location

USC HOAG

Newport Beach, California, 92663, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

UMASS Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Center for Oncology and Blood Disorders

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Center - University Health Network

Toronto, Ontario, M5G 1Z5, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Lymphoma; Pancreatic Neoplasms; Liver Neoplasms; Colonic Neoplasms; Lung Neoplasms; Bile Duct Neoplasms; Sarcoma; Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12; Carcinoma

Interventions

spartalizumab; pembrolizumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Liver Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Lewis Bender
• Organization: Intensity Therapeutics

LBender@intensityTherapeutics.com

2032217377

Study Officials

• Brian Schwartz, M.D.

  Intensity Therapeutics

  STUDY DIRECTOR

• Lillian Siu, M.D., FRCP

  Princess Margaret Hospital, Canada

  STUDY CHAIR

• Anthony El-Khoueiry, M.D.

  USC Norris and HOAG sites

  PRINCIPAL INVESTIGATOR

• Anthony J. Olszanski, M.D., RPh

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

• Nilofer Azad, M.D.

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

• Giles F Whalen, M.D.

  UMASS Memorial Medical Group

  PRINCIPAL INVESTIGATOR

• Matthew Ingham, M.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

• Luis Camacho, M.D.

  Center for Oncology and Blood Disorders

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: There were no masking and all patients received INT230-6 treatments.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 20, 2017
• Study Start: February 9, 2017
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: February 27, 2025
• Results First Posted: August 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); CA (1)