Two phase 1/2 trials of IAP0971 and IAE0972 in patients with locally-advanced or metastatic malignant tumors have dosed their first patients.
Trial Name: A Phase I/IIa Clinical Trial to Evaluate Effect of IAP0971 in Patients With Advanced Malignant Tumors
ClinicalTrials.gov Identifier: NCT05396391
Completion Date: November 30, 2024
Recruitment Status: Not yet recruiting
Sponsor: SUNHO (China) BioPharmaceutical CO., Ltd.
The first patients have been dosed in phase 1/2 trials of IAP0971 and IAE0972 (NCT05396391, NCT05396339) 2 first-in-class immunocytokines, for patients with treatment of locally-advanced or metastatic malignant tumors, according to SunHo BioPharmaceutical Co., Ltd.1
IAP0971 is the world's first PD1-IL15 immunocytokine to receive an investigational new drug approval from both FDA and The National Medical Products Administration and IAE0972 is the world's first EGFR-IL10 immunocytokine to do the same.
"We are excited for achieving this important milestone, which also marked the first step to what we hope will ultimately allow us to bring an innovative cancer immunotherapy to patients who otherwise do not respond to or become relapsed/refractory of current therapies", said Liusong Yin, MD, the executive president, and chief science officer of SunHo, in the press release.
IAP0971 is a PD1-IL15 immunocytokine designed to bind to the IL2/15Rβ and IL2/15Rγ expressed on both T cells and NK cells. It works to promote the proliferation and activation of these cells, without activation of Treg cells.
Additionally, the expression of PD1 on CD8-positive T cells in the tumor microenvironment is higher than what is found in peripheral blood and peripheral lymphoid organs, allowing the anti-PD1 antibody in IAP0971 to target IL15 into the tumor immune microenvironment, recruit, activate, reinvigorate immune cells, and achieve anti-tumor immunity.
Currently, IAP0971 has indications in lung cancer, cervical cancer, head and neck squamous cell carcinoma, liver cancer, lymphoma, and other locally-advanced, or metastatic malignant tumors.
The phase 1/2a study of IAP0971 will enroll around 140 patients to be included in 3 phases: dose-escalation (phase 1a), dose extension (phase 1b), and clinical exploration (phase 2a).2 In the phase 1a dose escalation portion of the trial, experts aim to characterize the safety and tolerability of IAP0971, find the dose-limiting toxicities (DLT) for each dose level studied, and to define the maximum tolerated dose (MTD) based on how often DLTs occur in each cohort during the DLT evaluation period.
After completion of phase 1a, phase 1b, the dose extension portion of the study, will be carried out in the MTD dose achieved from phase 1a. Once both phase 1a & 1b have finished and the recommended phase 2 dose (RP2D) is obtained, the clinical exploratory phase 2a portion of the trial will be carried out.
To be included in the trial, patients must be aged 18 to 80 years old with histologically or cytologically confirmed advanced or unresectable solid tumors. Patients may also have relapsed and/or refractory non-Hodgkin's lymphoma, who have progressed on or have been intolerant to standard treatment, or for whom no standard treatment exists, and an ECOG performance status of 0-1.
The primary end point for phase 1 of the trial is to evaluate the safety of IAP0971, finding the MTD, RP2D, incidence, and frequency of DLTs, and adverse events.
For phase 2a, primary end points include evaluating the effectiveness of IAP0971 until disease progression, assessed up to 3 years, and objective response rate (ORR). Secondary end points include pharmacokinetics, overall survival, incidence of anti-drug antibodies, progression-free survival, disease control rate, and more.
As for IAE0972, the EGFR-IL10 immunocytokine was designed to aid in immune cell exhaustion in current immunotherapy, as well as to lift the limitations of current EGFR-based monoclonal antibodies. In IAE0972, IL10 is a potent activator of antigen-specific CD8-positive T cells found within the tumor microenvironment. It is able to restore the tumor-killing activity of tumor-infiltrating lymphocytes by restoring the oxidative phosphorylation metabolism of terminally exhausted T cells.
Trial Name: A Phase I/IIa Clinical Trial to Evaluate Effect of IAE0972 in Patients With Advanced Malignant Tumors
ClinicalTrials.gov Identifier: NCT05396339
Completion Date: November 30, 2024
Recruitment Status: Not yet recruiting
Sponsor: SUNHO (China) BioPharmaceutical CO., Ltd.
The development of IAE0972 allows it to effectively activate the immune system to attack and kill EGFR-positive tumor cells. With this, the immunocytokine is able to solve the drug resistance, high skin toxicities, and other clinical problems currently found with existing drugs.
Indications of IAE0972 exist in colorectal cancer, head and neck squamous cell carcinoma, squamous non-small cell lung cancer, and other locally advanced or metastatic malignant tumors.
In the phase 1/2a study of IAP0971, the same 3 phases, dose escalation (phase 1a), dose extension (phase 1b), and clinical exploration (phase 2a) will be included in the trial.3 An estimated 120 participants will be enrolled to evaluate the safety, tolerability, pharmacokinetics and preliminary effectiveness of IAE0972 in patients with advanced malignant solid tumors.
Primary and secondary end points for this study are the same of those in the study of IAP0971 in this patient population.
Those enrolled must be aged between 18 and 80 years of age with histologically or cytologically confirmed locally advanced or metastatic solid malignant tumors, either refractory to standard therapy or for which no effective therapy was available. Further, patients must have measurable disease as determined by RECIST version 1.1 and documented by computed tomography and/or magnetic resonance imaging, an ECOG performance status of 0 or 1, a life expectancy of 12 weeks of greater, and resolution of all chemotherapy or radiation-related toxicities to ≤ grade 1.
"We focus on innovative immunocytokines to build the next leading global biopharma of immunotherapy, and to bring perceivable benefits and affordable medicine to patients worldwide, by innovation and collaboration," Yin added in the press release.
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