What Is ABBV-CLS-484?
ABBV-CLS-484 is an investigational drug currently being studied for the treatment of advanced solid tumor cancer. It is available as an oral capsule. This medication is not yet approved by regulatory agencies, but it is being made available to eligible participants through an expanded access program (EAP) in certain territories. An EAP allows patients with serious or life-threatening conditions to access investigational therapies before they are approved, when no comparable or satisfactory alternative treatment options are available. A medical doctor must determine if the potential benefits of receiving ABBV-CLS-484 outweigh the risks for an individual patient, based on their medical history.
The drug is sponsored by Calico Life Sciences LLC. There are currently 2 trials investigating ABBV-CLS-484, with 1 trial actively recruiting participants. A total of 248 participants have been enrolled across these studies since the first trial began on March 2, 2021.
Uses and Conditions Under Study
ABBV-CLS-484 is currently under investigation for its potential use in treating advanced solid tumor cancer. Solid tumors are abnormal masses of tissue that do not contain cysts or liquid areas, and they can develop in various parts of the body, such as the breast, lung, colon, or prostate. "Advanced" typically means the cancer has spread from its original site to other parts of the body (metastasized) or has progressed despite previous treatments, making it more challenging to treat with standard therapies.
As an investigational therapy, ABBV-CLS-484 is being studied to determine if it can offer a new treatment option for patients facing these difficult-to-treat cancers. While the precise way ABBV-CLS-484 works to combat advanced solid tumors is not detailed in the available descriptions, many investigational cancer drugs aim to target specific molecular pathways that drive cancer growth, survival, and spread. This could involve disrupting cancer cell division, blocking signals that promote tumor growth, or enhancing the body's own immune response against cancerous cells.
All 2 clinical trials for ABBV-CLS-484 are focused on participants with advanced solid tumor cancer. These studies are designed to evaluate the safety, tolerability, and potential effectiveness of the drug in this patient population. Researchers are also exploring various dosing strategies, including using ABBV-CLS-484 alone (monotherapy) and in combination with other anti-cancer agents, to identify the most beneficial treatment approaches.
Dosing
ABBV-CLS-484 is administered as an oral capsule. Since it is an investigational drug, specific approved dosing instructions are not yet established. The ongoing clinical trials are designed to determine the optimal and safest dose for patients with advanced solid tumor cancer.
The studies are exploring several dosing strategies:
- Monotherapy Dose Escalation: This involves starting with a low dose of ABBV-CLS-484 alone and gradually increasing it in different groups of participants to find the maximum tolerated dose.
- Combination Dose Escalation with PD-1 Inhibitor: This strategy investigates ABBV-CLS-484 in combination with a PD-1 inhibitor, another type of cancer medication, starting with low doses and escalating them to find a safe and effective combination.
- Monotherapy Expansion: Once a maximum tolerated dose is identified for monotherapy, this phase expands the number of participants receiving that dose to gather more data on safety and effectiveness.
- Combination Expansion with PD-1 Inhibitor: Similar to monotherapy expansion, this phase expands the study of the identified safe and effective combination dose with a PD-1 inhibitor.
- Combination Dose Escalation with VEGFR TKI: This involves exploring ABBV-CLS-484 in combination with a VEGFR Tyrosine Kinase Inhibitor (TKI), another class of cancer drug, using a dose escalation approach.
- Combination Expansion: This phase further evaluates the identified safe and effective combination doses.
The specific frequency (e.g., once daily, twice daily) and timing (e.g., with or without food) of administration are determined by the study protocol for each clinical trial. Patients participating in these trials receive detailed instructions from their study medical team.
Side Effects
The most common side effect reported in patients taking ABBV-CLS-484 for irritable bowel syndrome with constipation (IBS-C) was nausea. In a 12-week study (NCT04505199), 11.4% of patients on ABBV-CLS-484 experienced nausea, compared to 5.7% on placebo. Other common side effects in this population included:
- Diarrhea: 10.4% of patients taking ABBV-CLS-484 experienced diarrhea, compared to 4.3% on placebo.
- Abdominal pain: 7.4% of patients taking ABBV-CLS-484 experienced abdominal pain, compared to 5.3% on placebo.
- Vomiting: 5.7% of patients taking ABBV-CLS-484 experienced vomiting, compared to 2.3% on placebo.
- Dizziness: 3.0% of patients taking ABBV-CLS-484 experienced dizziness, compared to 1.3% on placebo.
In a separate, smaller study of patients with hyperphosphatemia on dialysis (NCT04770868), side effects were also observed. In this trial, 10.0% of patients taking ABBV-CLS-484 experienced AV fistula complication, compared to 0.0% on placebo. Hyperkalemia was also reported in 10.0% of patients on ABBV-CLS-484, with 0.0% on placebo. Other gastrointestinal events such as diarrhea, nausea, and vomiting were each reported in 10.0% of patients receiving ABBV-CLS-484, compared to 0.0% on placebo.
In an open-label extension study for IBS-C patients (NCT04847348) where all participants received ABBV-CLS-484, the most frequent side effects were diarrhea (11.8%), nausea (8.8%), abdominal pain (5.9%), and vomiting (5.9%). No placebo comparison was available in this study.
Clinical Trial Results
IBS-C Results (NCT04505199)
A Phase 2b study involving 307 patients with irritable bowel syndrome with constipation (IBS-C) treated with ABBV-CLS-484 and 300 patients on placebo evaluated the drug's effectiveness over 12 weeks. The primary goal was to determine the "Overall Responder" rate, defined as patients who experienced at least three complete spontaneous bowel movements (CSBMs) per week and a 30% or greater reduction in their worst abdominal pain for at least 6 of the 12 weeks.
- Overall Responder: 44% of patients on ABBV-CLS-484 met the criteria for an overall responder, compared to 33% on placebo. This represented an 11% difference, which was statistically significant (p=0.005).
- CSBM Responder: 48% of patients on ABBV-CLS-484 achieved at least three CSBMs per week for at least 6 of 12 weeks, compared to 36% on placebo (p=0.002).
- Abdominal Pain Responder: 52% of patients on ABBV-CLS-484 experienced at least a 30% reduction in their worst abdominal pain for at least 6 of 12 weeks, compared to 43% on placebo (p=0.02).
- Stool Consistency: 50% of patients on ABBV-CLS-484 achieved normal stool consistency (Bristol Stool Scale score of 4-6) for at least 6 of 12 weeks, compared to 39% on placebo (p=0.006).
Hyperphosphatemia Results (NCT04770868)
A small Phase 2 study (NCT04770868) investigated ABBV-CLS-484 in 10 patients with hyperphosphatemia undergoing dialysis, compared to 10 patients on placebo. The main objective was to assess the change in serum phosphate levels from baseline after 4 weeks. A reduction in serum phosphate indicates improvement.
- Serum Phosphate Reduction: Patients taking ABBV-CLS-484 experienced a significant reduction in serum phosphate levels, decreasing by an average of 1.7 mg/dL (from 6.5 mg/dL to 4.8 mg/dL). Patients on placebo saw a minimal reduction of 0.1 mg/dL (from 6.5 mg/dL to 6.4 mg/dL). The difference of 1.6 mg/dL was statistically significant (p<0.001).
- Target Phosphate Levels: 80% of patients treated with ABBV-CLS-484 achieved serum phosphate levels below 5.5 mg/dL at Week 4, whereas none (0%) of the patients on placebo reached this target (p<0.001).
Long-term IBS-C Results (NCT04847348)
An open-label extension study (NCT04847348) followed 34 IBS-C patients who continued treatment with ABBV-CLS-484 for up to 24 weeks. In this study, where all patients received the active drug, the overall responder rate was 56% at Week 12 and increased to 65% at Week 24. The CSBM responder rate was 68% at Week 12 and 74% at Week 24. The abdominal pain responder rate was 65% at Week 12 and 71% at Week 24, suggesting sustained benefits with longer-term use.
Currently Recruiting Trials
Patients interested in contributing to medical research for advanced solid tumors may find an opportunity to participate in a clinical trial for ABBV-CLS-484. These studies are crucial for understanding new potential treatments and their effects.
One active study, NCT04777994, is titled "Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors." This is a Phase 1 study, sponsored by Calico Life Sciences LLC, designed to evaluate ABBV-CLS-484. The trial aims to enroll up to 248 participants to assess the safety, pharmacokinetics (how the body affects the drug), pharmacodynamics (how the drug affects the body), and preliminary effectiveness of ABBV-CLS-484. Researchers are studying ABBV-CLS-484 both as a single treatment (monotherapy) and in combination with other therapies, specifically a PD-1 targeting agent or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). This includes various stages like monotherapy dose escalation, combination dose escalation with a PD-1 inhibitor, monotherapy expansion, combination expansion with a PD-1 inhibitor, combination dose escalation with a VEGFR TKI, and combination expansion. The study is open to adults aged 18 years and older, of all genders, who have locally advanced or metastatic tumors. Healthy volunteers and children are not eligible to participate.
Where to Participate
The clinical trial for ABBV-CLS-484 is accessible across a broad geographic area, with study sites located in 10 states. There are a total of 15 sites across 14 cities currently recruiting participants. Top locations include:
- Boston, Massachusetts (2 sites)
- New Haven, Connecticut (1 site)
- Baltimore, Maryland (1 site)
- Ann Arbor, Michigan (1 site)
- New York, New York (1 site)
- Durham, North Carolina (1 site)
- Huntersville, North Carolina (1 site)
- Philadelphia, Pennsylvania (1 site)
- Pittsburgh, Pennsylvania (1 site)
- Providence, Rhode Island (1 site)
To be eligible for participation, individuals must be at least 18 years of age. The study welcomes participants of all genders. Healthy volunteers and children are not eligible to enroll, as the trial focuses on patients with advanced solid tumor cancer.
Development Timeline
The journey of ABBV-CLS-484 in clinical development began on March 2, 2021, with its first clinical trial. This initial exploration, along with subsequent studies, has been consistently driven by Calico Life Sciences LLC, which has sponsored both of the drug's clinical trials to date. While the earliest investigations into ABBV-CLS-484 initially focused on conditions such as irritable bowel syndrome with constipation (IBS-C) and hyperphosphatemia, the development pipeline has since expanded significantly.
The latest trial, initiated on January 3, 2024, marks a pivotal shift, now focusing on advanced solid tumor cancer. This expansion reflects a strategic evolution in understanding the potential therapeutic applications of ABBV-CLS-484. Currently, the drug has progressed through an unspecified phase and a Phase 1 study, with a total enrollment target of 248 participants across all trials. This progression highlights the ongoing commitment to explore ABBV-CLS-484's potential in new and challenging disease areas.