- 32.4% of patients evaluable for efficacy achieved partial response or better; 76.5% of patients achieved disease control -
- Tumor shrinkage observed in both injected and uninjected lesions, indicating an abscopal effect -
ILLUMINATE-204 Key Findings:
- 37 patients dosed with 8 mg of tilsotolimod in combination with ipilimumab were evaluated for this update:
- 34 patients were evaluable for efficacy
- All patients were evaluable for safety
- Accrual is ongoing, with an additional 4 patients dosed
- Responses, including 2 Complete Responses (CR), were observed in 11 of the 34 evaluable patients (32.4%)
- Duration of response ranges from > 1 month to > 30 months, with 36% of responses ongoing
- Per RECIST v1.1, the Overall Response Rate (ORR) is 29.4%; one patient with an unconfirmed Partial Response (uPR) at the end of treatment assessment progressed due to a new lesion at the 3-month follow-up disease assessment
- Overall, 26 patients out of 34 evaluable for efficacy (76.5%) experienced disease control (CR, PR, or Stable Disease (SD))
- Analysis of spider plots show tumor shrinkage in both injected and uninjected lesions, indicating an abscopal effect
- Responding subjects include one patient with mucosal melanoma and one patient with acral melanoma, two forms of melanoma that are particularly difficult to treat
- Importantly, 2 of 5 patients with prior ipilimumab experience achieved responses, further demonstrating a signal that tilsotolimod has the potential to help overcome prior ipilimumab resistance
- The combination regimen continues to be generally well tolerated. 9/37 subjects (24.3%) had immune-related toxicities indicating that tilsotolimod + ipilimumab does not appear to add immune-related toxicity versus ipilimumab alone
- Injection-related toxicities were grade 1-2 transient fever and flu-like symptoms lasting <48 hours
- A RECIST v1.1 PR of > 2.5 years is ongoing in 1 patient treated with tilsotolimod 4 mg in combination with ipilimumab; and
- A RECIST v1.1 CR of > 1 year is ongoing in 1 patient treated with tilsotolimod 16 mg in combination with pembrolizumab.
“The results from this combination are among the most promising we have seen in this challenging population of metastatic melanoma patients who have not benefited from front-line immunotherapy,” stated
The ILLUMINATE-204 trial is comprised of two distinct patient populations, patients who are ipilimumab naïve (N=up to 40; Primary Efficacy Endpoint Population) and patients who have ipilimumab experience (N=up to 20; Secondary Efficacy Endpoint Population). Of the initial 34 patients evaluable for efficacy, evaluations 9 of 29 patients from the Primary Efficacy Endpoint Population and 2 of 5 patients from the Secondary Efficacy Endpoint Population achieved responses.
Indications of the specific mechanism of action for tilsotolimod were suggested in the clinical responses observed in patients whose tumor HLA-ABC RNA (MHC class I) expression was low at baseline. As recently articulated by Rodig, et al.1 robust MHC class I expression is required for anti-CTLA-4 activity. These findings suggest that combining tilsotolimod with ipilimumab may overcome this resistance mechanism and, therefore, enhance the overall response rate compared to that expected with ipilimumab alone.
“The continued positive results from this trial, a response rate substantially higher than expected with ipilimumab alone, and anti-tumor activity in both injected and uninjected lesions are exciting. These reinforce our conviction that tilsotolimod may overcome an immunosuppressive tumor microenvironment and, in combination with ipilimumab, could provide a treatment option when anti PD-1 therapy fails these patients,” stated Dr.
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About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda®** (pembrolizumab) or Opdivo®* (nivolumab) has failed. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy®) or pembrolizumab (Keytruda®) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.
For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.
About Metastatic Melanoma
Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths.
Harnessing the approach of the earliest researchers in immunotherapy and the Company’s vast experience in developing proprietary immunology platforms, Idera’s lead development program is focused on priming the immune system to play a more powerful role in fighting cancer, ultimately increasing the number of people who can benefit from immunotherapy.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical fact, included or incorporated in this press release, including statements regarding the Company's strategy, future operations, collaborations, intellectual property, cash resources, financial position, future revenues, projected costs, prospects, clinical trials, plans, and objectives of management, are forward-looking statements. The words "believes," "anticipates," "estimates," "plans," "expects," "intends," "may," "could," "should," "potential," "likely," "projects," "continue," "will," and "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
*Yervoy (ipilimumab) and Opdivo (nivolimumab) are registered trademarks of
**Keytruda (pembrolizimab) is a registered trademark of
1 Rodig, S., et al., MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma. Sci. Transl. Med. 10, eaar3342 (2018).
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Source: Idera Pharmaceuticals, Inc.