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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

4458 - Phase 1/2 evaluation of intratumoral INT230-6 for the treatment of solid tumors

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Clinical Research

Tumour Site

Presenters

Anthony El-Khoeuiry

Citation

Annals of Oncology (2018) 29 (suppl_8): viii400-viii441. 10.1093/annonc/mdy288

Authors

A. El-Khoeuiry1, L.L. Siu2, N. Azad3, I.B. Walters4, L. Bender4, L. Kamen4, A.J. Olszanski5

Author affiliations

  • 1 Phase 1 Program, USC Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 2 Phase 1 Program, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 3 Phase 1 Clinical Trials Group, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 21231 - Baltimore/US
  • 4 Clinical research, Intensity Therapeutics, 06880 - Westport/US
  • 5 Phase 1 Developmental Therapeutics Program, Fox Chase Cancer Center, 19111-2497 - Philadelphia/US
More

Resources

Abstract 4458

Background

INT230-6 is a formulation of cisplatin and vinblastine with an amphiphillic penetration enhancer to improve dispersion and diffusion into cancer cells. This is the first product designed for selective delivery into tumors with the potential to deliver high payload levels directly into cancer cells while sparing healthy cells. In colon 26 animal models, injection into a sentinel lesion led to tumor necrosis, recruitment of dendritic cells into the tumor and activation of CD4 and CD8 T-cells. Injected tumors experienced high rates of complete response (up to 80%). Importantly, untreated lesions distal to the injection site also responded. Efficacy was synergistic when combined with checkpoint inhibitors.

Methods

Initial cohort enrolled subjects with advanced solid tumors with superficial lesions amenable to local injection. INT230-6 was administered intratumorally at a ratio of 1ml for each 4 cubic cm of tumor volume, once each month for a total of 5 cycles. Both the maximal dose into one tumor and the total dose (over multiple lesions) could be escalated on repeat cycles if no DLTs. Patients were monitored for safety weekly. Pharmacokinetic(Pk) samples and peripheral blood were collected for flow cytometry and circulating cytokines. Subsequent cohorts of twice monthly injections into superficial tumors and monthly injection into deep tumors commenced after comprehensive review of safety data in superficial tumors.

Results

Thirteen subjects were treated with either melanoma, SCC, ovarian, chordoma, cholangiocarcinoma or H&N into single or multiple lesions. Pk analysis revealed negligible amounts of reduced platinum and vinblastine in blood, suggesting retention in the tumor compartments. No DLTs or drug related SAEs were reported. The most frequent adverse event was grade 1 or 2 injection site pain, or other local symptom (infection or blister). Subjectively, some injected lesions were noted to change as soon as 1 week with flattening and areas of necrosis.

Conclusions

INT230-6 was safe when administered locally to tumors at doses given. Updated results will be presented including biomarker and response data. Additional cohorts including higher drug concentrations and combination with an anti-PD1 antibody.

Clinical trial identification

NCT:03058289.

Legal entity responsible for the study

Ian B. Walters, MD.

Funding

Intensity Therapeutics.

Editorial Acknowledgement

Disclosure

A. El-Khoeuiry, L.L. Siu, N. Azad, A.J. Olszanski: Funding to institutions: Intensity Therapeutics. I.B. Walters: Employee and stockholder: Intensity Therapeutics. L. Bender: Founder and CEO of Intensity Therapeutics, named on the patents, stock holder and employee of the company which manufactures the product being studied. L. Kamen: Consultant and stock owner: Intensity therapeutics.

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