Background on the INVINCIBLE-3 Trial
Trial Name: A Multicenter, Randomized, Phase 3 Study to Assess the Efficacy and Safety of INtratumorally Administered INT230-6 (SHAO, VINblastine, CIsplatin) Compared With US Standard of Care in Adults With Locally Recurrent, InoperaBLE, or Metastatic Soft Tissue Sarcomas (INVINCIBLE-3)
ClinicalTrials.gov Identifier: NCT06263231
Sponsor: Intensity Therapeutics Inc.
Recruitment Contact: Kimberly Guedes, RN, M.B.A, (203) 293-4224, KGuedes@intensitytherapeutics.com and Lewis H Bender, MS, MA, MBA, (203) 221-7377, LBender@intensityTherapeutics.com
Completion Date: December 2028
The phase 3 INVINCIBLE-3 study (NCT06263231) evaluating INT230-6 as monotherapy for the treatment of patients with metastatic sarcoma has dosed its first US patient.1
INT230-6 is the lead proprietary investigational product candidate from Intensity Therapeutics. Designed for direct intratumoral injection, INT230-6 was discovered using the proprietary DfuseRx℠ technology platform and is made of cisplatin, vinblastine, and a penetration enhancer molecule (SHAO). This aids in distributing potent cytotoxic drugs throughout tumors for dispersal into cancer cells. Additionally, each of these 3 agents stay in the tumor, which leads to a favorable safety profile.
A bolus of neoantigens specific to the malignancy are also released with INT230-6. This leads to antitumor activity and immune system engagement.
"We have now dosed our first patient in the US and have filed regulatory documents to initiate this trial in Canada and Europe. Over the next several months, we anticipate initiating sites in eight countries,” said Lewis H. Bender, Intensity Therapeutics' founder, chairman, and chief executive officer, in a press release. “Sarcoma is a deadly cancer with a median overall survival following second- and third-line drug treatments of between 10 and 15 months."
The global, multicenter, randomized, phase 3, superiority study is testing treatment with INT230-6 alone vs the investigator's choice of 3 current standard-of-care (SOC) systemic chemotherapy drugs in second- or third-line metastatic, recurrent, or inoperable soft tissue sarcomas.2
Approximately 333 patients will be enrolled in the study and subtypes of soft tissue sarcomas being enrolled include leiomyosarcoma, liposarcoma, and undifferentiated pleomorphic sarcoma. For every 3 patients treated, 2 patients will be given treatment with INT230-6, and 1 will receive the SOC.
Enrollment is open to patients aged 18 years and older with histologically proven, unresectable, locally advanced, or metastatic soft tissue sarcoma. Patients are required to have measurable disease per RECIST 1.1 criteria, have at least 1 target tumor suitable for injection using routine image guidance ≥ 2 cm measurable by CT or MRI, have an ECOG performance status of 0 to 2, and have received at least 1 line of therapy for their sarcoma. Additionally, patients must have progressed following anthracycline-based or alternative standard therapies, except if medically contraindicated or refused.
Additional criteria states that the patient must have adequate organ function as defined by screening laboratory values and that patients are not eligible if they have received more than 2 prior regimens for unresectable, locally advanced, or metastatic soft tissue sarcoma.
The study’s primary end point is overall survival.
In a prior phase 1/2 trial of INT230-6, the agent demonstrated tumor-killing and immune-activating properties. An increased survival was also observed in patients with metastatic disease.1
"During our phase 1/2 metastatic dose escalation study, in a sarcoma population that had progressed following a median of 3 lines of therapy, we reported a median overall survival of 21.3 months with our drug alone. Patients, their caregivers, and physicians worldwide desperately need improved treatment options, and we are excited to have finally begun testing our new approach in phase 3. I want to take this opportunity to thank our dedicated team for getting us to this tremendous milestone,” said Bender in the press release.
REFERENCES:
1. Intensity Therapeutics, Inc. announces first patient dosed in its global randomized, phase 3 study (INVINCIBLE-3) in metastatic soft tissue sarcoma. News release.Intensity Therapeutics, Inc. July 9, 2024. Accessed July 9, 2024. https://tinyurl.com/bdz6zdt4
2. A study to investigate efficacy & safety of INT230-6 compared to US standard of care in adults with soft tissue sarcomas (INVINCIBLE-3) (INVINCIBLE-3). ClinicalTrials.gov. Accessed July 9, 2024. Updated June 21, 2024. https://clinicaltrials.gov/study/NCT06263231?tab=table
