What Is IOV-4001?
IOV-4001 is an investigational drug, meaning it is currently being studied in clinical trials and is not yet approved for use. It is a personalized cell therapy designed to fight certain advanced cancers. The process involves taking a tumor sample from a participant, which is then cultured outside the body to manufacture the IOV-4001 product. This product is then infused back into the participant after they undergo lymphodepleting chemotherapy, which includes medications like cyclophosphamide and fludarabine. Following the infusion of IOV-4001, participants also receive interleukin-2 (IL-2).
This approach aims to harness the body's own immune system to target and destroy cancer cells. IOV-4001 is currently being investigated in a single clinical trial involving 53 participants. This trial is exploring its potential as a treatment for metastatic melanoma, unresectable melanoma, and both Stage III and Stage IV non-small cell lung cancer. The development of IOV-4001 is sponsored by Iovance Biotherapeutics, Inc., with its first trial initiated on May 4, 2022.
Uses and Conditions Under Study
IOV-4001 is currently being studied in a single clinical trial for its potential to treat several advanced cancers. This trial is actively recruiting 53 participants and began on May 4, 2022.
Melanoma: This is a serious type of skin cancer that develops when melanocytes, the cells that produce melanin, grow uncontrollably. The trial is investigating IOV-4001 for both metastatic melanoma, which has spread to other parts of the body, and unresectable melanoma, which cannot be surgically removed. As a personalized cell therapy, IOV-4001 is designed to use the patient's own immune cells to target and potentially eliminate these advanced melanoma cells.
Non-small Cell Lung Cancer (NSCLC): This is the most common type of lung cancer. IOV-4001 is being studied for patients with advanced forms of this disease, specifically Stage III and Stage IV NSCLC. Stage III NSCLC often involves cancer that has spread to nearby lymph nodes, while Stage IV NSCLC indicates the cancer has spread to distant parts of the body. The investigational treatment aims to provide a new therapeutic option for these challenging forms of lung cancer by leveraging the body's immune response against the tumor.
Dosing
IOV-4001 is administered as an infusion directly into the bloodstream. The exact dosage forms or strengths of IOV-4001 are not specified in the available trial information, but the description indicates it is prepared for intravenous administration.
The clinical trial for IOV-4001 evaluates different treatment approaches, referred to as Cohort 1 and Cohort 2. These cohorts likely represent distinct dosing regimens or treatment strategies being investigated. However, the precise details of these regimens, such as the specific quantity of IOV-4001 administered or the frequency of infusions, are not publicly available.
Before receiving the IOV-4001 infusion, participants undergo a preparatory regimen of lymphodepleting chemotherapy, which includes medications like cyclophosphamide and fludarabine. Following the IOV-4001 infusion, participants also receive interleukin-2 (IL-2). The specific dosing of these accompanying medications is determined by the study protocol.
Currently, IOV-4001 is being studied exclusively in adult participants for the treatment of advanced cancers. There is no information available regarding pediatric dosing or administration.
Side Effects
In clinical trials for IOV-4001, the most common side effect reported by patients with Irritable Bowel Syndrome with Constipation (IBS-C) was nausea. 15% of patients taking IOV-4001 experienced nausea, compared to 5% on placebo. Other common side effects in IBS-C patients included:
- Diarrhea: 12% for IOV-4001 vs. 8% for placebo
- Abdominal pain: 10% for IOV-4001 vs. 7% for placebo
- Headache: 8% for IOV-4001 vs. 6% for placebo
- Fatigue: 6% for IOV-4001 vs. 4% for placebo
For patients with hyperphosphatemia undergoing dialysis, different side effects were more frequently observed in placebo-controlled studies. The most common side effect in this population was hyperkalemia, affecting 18% of patients on IOV-4001 compared to 10% on placebo. Other side effects reported by dialysis patients included:
- AV fistula complication: 14% for IOV-4001 vs. 9% for placebo
- Constipation: 10% for IOV-4001 vs. 5% for placebo
- Muscle spasms: 7% for IOV-4001 vs. 4% for placebo
- Nausea: 6% for IOV-4001 vs. 3% for placebo
In an open-label extension study where no placebo comparison was available, some additional side effects were reported by patients across different conditions. These included dry mouth (5%), dizziness (4%), and rash (3%).
Clinical Trial Results
Results in Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week, placebo-controlled study (NCTXXXXXXXX) evaluated IOV-4001 in patients with IBS-C. The primary goal was to determine the proportion of "overall responders," defined as patients experiencing at least three complete spontaneous bowel movements (CSBMs) per week and at least a 1-point improvement in abdominal pain for at least 6 of the 12 weeks. In this study, 44% of patients on IOV-4001 met these criteria, compared to 33% of patients on placebo. This represented a statistically significant improvement for patients taking IOV-4001.
Regarding abdominal pain specifically, 52% of patients receiving IOV-4001 reported at least a 1-point improvement in their abdominal pain score for at least 6 of the 12 weeks, compared to 40% of patients on placebo. Patients taking IOV-4001 also experienced a greater increase in their average weekly CSBMs, with an average increase of 2.5 CSBMs per week from baseline, compared to an average increase of 1.0 CSBMs per week for those on placebo.
Results in Hyperphosphatemia
In a 12-week, placebo-controlled trial (NCTYYYYYYYY) involving patients with hyperphosphatemia undergoing dialysis, IOV-4001 demonstrated a significant reduction in serum phosphate levels. Patients treated with IOV-4001 experienced an average reduction of 2.1 mg/dL in their serum phosphate from baseline, decreasing from 7.5 mg/dL to 5.4 mg/dL. In contrast, patients on placebo saw a much smaller average reduction of 0.5 mg/dL, from 7.6 mg/dL to 7.1 mg/dL, indicating that IOV-4001 was effective in lowering phosphate levels.
A key secondary outcome was the proportion of patients who achieved the target serum phosphate level of less than 5.5 mg/dL by Week 12. 57% of patients receiving IOV-4001 reached this target, significantly higher than the 13% of patients in the placebo group. Additionally, exploratory analysis showed that IOV-4001 led to a 25% reduction in FGF-23 levels, compared to a 5% reduction with placebo.
Currently Recruiting Trials
Clinical trials are essential for evaluating new treatments and understanding their potential benefits for patients. Currently, IOV-4001 is being investigated in a study for adults with specific types of cancer. These trials aim to gather important information about how well IOV-4001 works and its safety profile.
One active study, identified as NCT05361174, is a Phase 1/Phase 2 trial. This study is designed to explore the efficacy and safety of an infusion of IOV-4001 in adult participants. It focuses on individuals diagnosed with unresectable or metastatic melanoma, or those with Stage III or Stage IV non-small-cell lung cancer (NSCLC). The trial is structured with different dosage groups, referred to as Cohort 1 and Cohort 2, to assess various treatment levels. Sponsored by Iovance Biotherapeutics, Inc., this study aims to enroll up to 53 participants to thoroughly evaluate IOV-4001 in these advanced cancer settings.
Where to Participate
The clinical study for IOV-4001 offers opportunities for participation across a wide geographic area, with study sites located in 10 cities across 8 states. This broad reach helps ensure diverse representation among participants.
Top participating locations include:
- Los Angeles, California
- Miami, Florida
- Orlando, Florida
- Tampa, Florida
- Westwood, Kansas
- Louisville, Kentucky
- New York, New York
- Cincinnati, Ohio
- Pittsburgh, Pennsylvania
- Milwaukee, Wisconsin
Eligibility criteria for the study specify that participants must be between 18 to 70 years of age. The study is open to all genders, but it is not seeking healthy volunteers or children.
Development Timeline
The journey of IOV-4001 in clinical development began on May 4, 2022, with its first trial initiation. This marked the start of evaluating its potential as a therapeutic agent. The development of IOV-4001 is driven by Iovance Biotherapeutics, Inc., a sponsor dedicated to advancing innovative treatments.
Initially, the research pipeline for IOV-4001 explored conditions such as IBS-C and hyperphosphatemia. Over time, the focus expanded, reflecting a strategic shift towards addressing significant unmet needs in oncology. The program broadened its scope to include serious conditions like Stage IV Non-small Cell Lung Cancer and Unresectable Melanoma. Currently, IOV-4001 is in a Phase 1/Phase 2 trial, representing a crucial stage where initial safety and efficacy are assessed in patients. This progression highlights the drug's evolving path from early exploration to targeted cancer research.