INTENSITY THERAPEUTICS, INC. Abstract 1574238: INTRATUMORAL INT230-6 (CISPLATIN, VINBLASTINE, SHAO) ALONE OR WITH IPILIMUMAB PROLONGED SURVIVAL WITH FAVORABLE
SAFETY AND IMMUNE ACTIVATION IN ADULTS WITH REFRACTORY SARCOMAS (NCT 03058289)
Authors: Christian Frederick Meyer1, Matthew Ingham2, James S Hu1, Jacob Stephen Thomas3, Anthony B. El-Khoueiry3, Diana L. Hanna3, Giles Francis Whalen4, Luis H. Camacho5, Anthony J. Olszanski6, Nilofer Saba Azaz1, Ian B. Walters7, Lewis H. Bender7. Albiruni Ryan Abdul Razak8; Lillian L. Siu8,
1. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; 2. Columbia University Irving Medical Center, New York, NY; 3. Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; 4. University of Massachusetts Memorial Medical Center, Worcester, MA, 5. Center for Oncology and Blood Disorders,
Houston, TX; 6. Fox Chase Cancer Center, Philadelphia, PA; 7. Intensity Therapeutics, Inc., Westport, CT; 8. Princess Margaret Cancer Centre, University Health Network, Toronto, ON;
BACKGROUND AND METHODS
- Metastatic soft tissue sarcomas are a deadly and diverse group of solid tumors derived from mesenchymal cells; highly toxic chemotherapy provides only limited benefit and immunotherapy to date has shown to be mostly ineffective as treatment.
- A new localized method of cancer killing has been created using a novel formulation (INT230-6)consisting of cisplatin (CIS),vinblastine (VIN) and a diffusion enhancer molecule (SHAO) specifically designed to enable drug dispersion throughout a tumor and cancer cell penetration via a passive process following intratumoral (IT) injection.
- The drug causes apoptosis and necrosis resulting in dendritic & T-cells flux to the tumor.
- IT-01is an open-label phase 1/2 study in adults with locally advanced, unresectable or metastatic solid tumors, including sarcoma. INT230-6 dose was set by tumor diameter or volume and was given IT Q2W for up to 5 doses alone or with IPI IV at 3mg/kg Q3 weeks for 4 doses. Maintenance dosing of INT230-6 was Q9W.
- Previously reported results showed INT230-6 alone induced tumor regression in uninjected lesions1 (an abscopal effect) in multiple cancer types both immunogenic (hot) and non-immunogenic(cold) with T-cellinfiltrates identified within the tumor.
Primary Outcome Measures for Phase 1/2 study: Assess the preliminary efficacy of INT230-6 alone or in combination with immunotherapy as measured by overall survival and disease control rate in specific cancer types.
INT230-6is a locally delivered cytotoxic treatment leading to a systemic immune response in hot or cold tumors, and is a new way to treat sarcoma
Compared to synthetic controls2 INT230-6 alone extended survival in refractory soft tissue sarcoma subjects by about 14.9 months with favorable safety; using higher dose relative to presenting tumor burden OS is increased and may be further improved with the addition of IPI
CONTACT: Intensity Therapeutics, Inc. Lewis H. Bender
Email: lbender@intensitytherapeutics.com Phone: (203) 221-73771 Enterprise drive, Shelton, CT 06484
Website: www.Intensitytherapeutics.com
SARCOMA SUBJECTS DEMOGRAPHICS
1 | OVERALL SURVIVAL EFFICACY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
mOS not yet reached | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
mOS not yet reached | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.8 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Probability 0.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.7 | mOS: 649 days (143, NR) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Survival | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.3 | mOS 205 days | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.2 | mOS = median overall survival | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
0 | 100 | 200 | 300 Days | 400 | 500 | 600 | 700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INT230-6, n=15 | INT230-6 dosed >40% TTB, n=11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INT230-6 + IPI, n=14 | Control, n=56 (synthetic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Censored |
Dosing relative to presenting total tumor burden (TTB) show increased survival with higher drug volume loaded for sarcoma subjects administered INT230-6 with or without ipilimumab compared to a synthetic control2. Abscopal responses for INT230-6 alone (previously reported) were primarily in subjects dosed ≥ 40% of TTB. The disease control rate (DCR; Stable disease + partial response + complete response divided by number of subjects) for the all-treated population (those who received at least one dose of INT230-6) was 93% for monotherapy and 86% for the ipi combo. For combo, one subject had yet to reach first timepoint for SD.
Additional Outcome Measures for Phase 1/2: | Demographics (Datalock) | INT230-6 (n=15) | INT230-6 + IPI (n=14) | |
Age (median, range) | 64 (41.9-76.1) | 63.2 (33-82.1) | ||
Characterize the overall safety of INT230-6 alone or in combination with immunotherapy | ||||
by the rate of grade 3 or higher adverse events (AEs) attributed to the study treatments. | Gender | 73.3% male | 50% male | |
Characterize the pharmacokinetic (PK) profile of multiple doses of the three INT230-6 | ECOG | 0 (13.3%), 1 (80%) 2 (6.7%) | 0 (42.9%) 1 (57.1%) | |
Median # of prior therapies, (range) | 3 (0-8) | 5 (0-9) | ||
components (CIS, VBL, and SHAO) after single and then multiple IT tumor site injections. | ||||
# of tumors injected (% deep) | 120 (47.5) | 127 (69.4%) | ||
SAFETY | ||||||||||||||
INTRATUMORAL INJECTION OF INT230-6 LEADS TO DRUG DISPERSION THROUGHOUT THE | The vast majority of TEAEs related to the drug regimen were grade 1 or 2; two monotherapy and one | |||||||||||||
combination subject had a grade 3 AE. There were no related grade 4 or grade 5 drug regimen AEs in either arm | ||||||||||||||
LESION AND HIGH PERCENTAGES OF NECROSIS IN LARGE HUMAN TUMORS | ||||||||||||||
Tumor death is dependent on total dose given per treatment (images below are from a neoadjuvant study in breast cancer) | Treatment-Emergent Adverse Events (TEAEs), n (%), Considered Related To Drug Regimen by MedDRA | |||||||||||||
3.9 cm invasive BC tumor: | Dose is set by a tumor's | Coded SOC/PT - All Sarcoma Treated Population 3 or more events for category. | ||||||||||||
4.4 cm invasive BC tumor: June 16 | Monotherapy | INT230-6 + IPI | ||||||||||||
volume or diameterMay 27 | ||||||||||||||
Sarcoma | Sarcoma | |||||||||||||
May 6 | May | 13 | May | 20 | ||||||||||
Data base locked as of February 22, 2023 | (N=15) | (N=14) | ||||||||||||
Injection #1: | Injection #2: | Surgery | One injection Dose 21.3 cc | Surgery | ||||||||||
Total # of TEAEs Related to Study Drug | 107 | 76 | ||||||||||||
Dose 7.4 cc | Dose 14.8 cc | |||||||||||||
Tumor post surgery | Subjects With at Least One TEAEs Related to Study Drug | 14 (93.3%) | 12 (85.7%) | |||||||||||
Tumor post surgery | Tumor Extent | |||||||||||||
Localized tumor-related pain | 12 (80.0%) | 6 (42.9%) | ||||||||||||
Extent of | Fatigue | 6 (40.0%) | 5 (35.7%) | |||||||||||
Nausea | 7 (46.7%) | 4 (28.6%) | ||||||||||||
Necrosis | Vomiting | 5 (33.3%) | 3 (21.4%) | |||||||||||
within Tumor | ||||||||||||||
Decreased appetite | 5 (33.3%) | 2 (14.3%) | ||||||||||||
Pruritus | 0 | 3 (21.4%) | ||||||||||||
Rash maculo-papular | 0 | 3 (21.4%) | ||||||||||||
Final Pathology (significant necrosis ~85%) | Final Pathology (significant necrosis >95%) | Anaemia | 3 (20.0%) | 2 (14.3%) |
Residual cancer is mostly ghost cells | 2. Synthetic control: Using survival results based on Royal Marsden Hospital scoring (RMHS) reported in Subbiah V, et al. Sci | |
1. Thomas, J. S, et. al. SITC 2021 Abstract Number: 501 | Rep. 2016;6:35448, we created a synthetic control (n=56) using our study's sarcoma subject's RMHS parameters |
INCREASE IN IMMUNE BIOMARKERS IN SARCOMA | |||
C1D0 | Marker | Color | C2D0 |
CD4+ T-cell | |||
CD8+ T-cell | |||
Cancer (DAPI) |
Chondrosarcoma patient
Biopsies taken pretreatment cycle 1 day 0 (C1D0) and Day 28 (C2D0) for immunohistochemistry analysis. There was a notable reduction in cancer cells (blue) post 2 doses of INT230-6 at day 28 and an increase CD4+ (yellow) CD8+ T-cells.
FUTURE DIRECTIONS: PHASE 3 STUDY DESIGN
~65 sites in 8 countries including US Intent to treat population: 332 patients
Two interim looks at 50% and 75% of events: test for futility and efficacy
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Intensity Therapeutics Inc. published this content on 01 November 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 02 November 2023 14:36:43 UTC.
