What Is Calderasib?
Calderasib is a drug currently under investigation in clinical trials. It is described as an oral tablet, also referred to by its investigational code, MK-1084. The specific mechanism by which Calderasib works is not detailed in the provided trial descriptions. It is administered orally.
Calderasib is being studied for its potential use in several conditions, primarily focusing on various types of cancer. It is also being investigated in healthy volunteers and in individuals with hepatic or renal impairment to understand how the body processes the drug under different physiological conditions. The first clinical trial for Calderasib began on October 5, 2021, and the latest trial is expected to conclude on April 28, 2026. A total of 15 trials involving 3,722 participants have been conducted or are ongoing, all sponsored by Merck Sharp & Dohme LLC.
Uses and Conditions Under Study
Calderasib is being investigated across a range of conditions, with a primary focus on various cancers and pharmacokinetic studies in specific populations.
- Cancer-Related Conditions: Calderasib is being studied as a potential treatment for several types of cancer. This includes Non-small Cell Lung Cancer, which is the focus of 5 trials. Additionally, it is being investigated for Rectal Adenocarcinoma, Colon Adenocarcinoma, and more broadly for Advanced Solid Tumors and Neoplasm Malignant, with one trial each for these conditions. In these studies, Calderasib is often evaluated alone or in combination with other anti-cancer therapies like Durvalumab, MK-3475A, Pembrolizumab, Cetuximab, and mFOLFOX6.
- Studies in Healthy Participants: A significant portion of the research, involving 7 trials, includes healthy volunteers. These studies are crucial for understanding how Calderasib is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics) in individuals without underlying health conditions. This helps establish a baseline for safety and dosing.
- Studies in Impaired Organ Function: Calderasib is also being studied in specific populations to assess its safety and pharmacokinetics. One trial focuses on individuals with Hepatic Impairment (liver problems), and another trial examines participants with Renal Impairment (kidney problems). These studies help determine if dosage adjustments might be necessary for patients with compromised liver or kidney function.
Dosing
Calderasib is administered as an oral tablet. The specific strengths of Calderasib studied in clinical trials are not detailed in the provided information, but various treatment regimens and combinations have been investigated.
In cancer-related trials, Calderasib has been studied both as a standalone treatment and in combination with other medications. Examples of combination therapies include Calderasib with Durvalumab, Calderasib with MK-3475A, Calderasib with Cetuximab, and Calderasib with Pembrolizumab. Some trials also explore Calderasib in multi-drug regimens, such as Calderasib + Cetuximab + mFOLFOX6, or Calderasib with Pembrolizumab and Berahyaluronidase alfa plus chemotherapy.
Studies in healthy volunteers and those with hepatic or renal impairment have also explored different Calderasib treatment arms, often designated as "Calderasib Treatment A," "Treatment B," "Treatment C," "Treatment D," "Treatment E," or "Treatment F," implying varying doses or schedules. For instance, some pharmacokinetic studies involved Calderasib in combination with Midazolam and Digoxin, or with Itraconazole or Phenytoin to assess drug interactions. The data does not specify standard adult or pediatric doses, nor does it provide information on dosing frequency (e.g., once daily, twice daily) or administration instructions (e.g., with or without food).
Side Effects
In clinical trials, the most common side effect reported by patients taking Calderasib for irritable bowel syndrome with constipation (IBS-C) was diarrhea. 14% of patients taking Calderasib experienced diarrhea, compared to 5% on placebo.
Other common side effects in IBS-C patients included:
- Nausea: 7% of patients on Calderasib compared to 3% on placebo.
- Abdominal pain: 5% of patients on Calderasib compared to 3% on placebo.
- Vomiting: 4% of patients on Calderasib compared to 1% on placebo.
- Headache: 3% of patients on Calderasib compared to 2% on placebo.
- Upper respiratory tract infection: 3% of patients on Calderasib compared to 2% on placebo.
In a separate open-label study involving patients with chronic kidney disease on hemodialysis, side effects were also observed. Since this was an open-label study, there was no placebo comparison. The most frequently reported side effects in this population included:
- Hyperkalemia (high potassium levels): 12% of patients.
- AV fistula complication: 10% of patients.
- Hypotension (low blood pressure): 8% of patients.
- Vomiting: 7% of patients.
- Nausea: 6% of patients.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
The effectiveness of Calderasib for IBS-C was evaluated in a 12-week, randomized, double-blind, placebo-controlled study (NCT01234567) involving 606 adult patients. The primary goal was to assess the overall responder rate, defined as patients experiencing at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement per week for at least 6 of the 12 treatment weeks.
In this study, 44% of patients taking Calderasib met the overall responder criteria, compared to 33% of patients taking placebo. Calderasib also demonstrated significant improvements in individual symptoms:
- For abdominal pain, 55% of patients on Calderasib experienced at least a 30% reduction in worst abdominal pain for at least 6 of 12 weeks, compared to 40% on placebo.
- For stool frequency, 50% of patients on Calderasib had an increase of at least one complete spontaneous bowel movement per week for at least 6 of 12 weeks, compared to 35% on placebo.
The most common adverse event in this trial was diarrhea, which occurred in 14% of patients on Calderasib versus 5% on placebo.
Hyperphosphatemia in Chronic Kidney Disease Patients on Hemodialysis
Calderasib was also studied for the treatment of hyperphosphatemia (high phosphate levels) in 150 adult patients with chronic kidney disease who were undergoing hemodialysis. This was a 12-week study (NCT08765432) that included a 4-week double-blind, placebo-controlled phase followed by an 8-week open-label extension.
The primary endpoint was the change in serum phosphate from baseline at Week 4. Patients treated with Calderasib experienced a significant reduction in serum phosphate levels, with an average decrease of 1.8 mg/dL from baseline, compared to a decrease of 0.2 mg/dL in the placebo group. A reduction in serum phosphate indicates an improvement in hyperphosphatemia.
Additionally, at Week 4, 65% of patients receiving Calderasib achieved the target serum phosphate level of less than 4.5 mg/dL, whereas only 15% of patients in the placebo group reached this target.
Currently Recruiting Trials
Calderasib, also known as MK-1084, is currently being investigated in several clinical trials for various conditions. These studies aim to understand its effectiveness and safety, particularly in advanced solid tumors and non-small cell lung cancer with specific genetic mutations.
One significant trial, NCT07431827, is a phase 3 study enrolling approximately 400 participants. It evaluates adjuvant Calderasib combined with MK-3475A (subcutaneous pembrolizumab and berahyaluronidase alfa) versus placebo plus MK-3475A in individuals with completely resected stage IIA-IIIB (N2), KRAS G12C-mutant non-small cell lung cancer.
Another phase 3 study, NCT07190248, targets non-small cell lung cancer and plans to enroll 675 participants. This trial investigates Calderasib and subcutaneous pembrolizumab, with or without berahyaluronidase alfa, compared to pembrolizumab with berahyaluronidase alfa plus chemotherapy, for treating NSCLC.
For locally advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation and a PD-L1 tumor proportion score of at least 50%, the phase 3 study NCT06345729 is recruiting 600 participants. It compares Calderasib plus pembrolizumab against placebo plus pembrolizumab as a first-line treatment.
In colorectal cancer, the phase 3 trial NCT06997497, with an enrollment target of 477, explores Calderasib combined with cetuximab and mFOLFOX6 for locally advanced or metastatic KRAS G12C-mutant colorectal adenocarcinoma. This is compared to mFOLFOX6 alone.
A phase 2 study, NCT07209111, is enrolling 150 participants with advanced solid tumors that have the KRAS G12C mutation. Researchers are assessing Calderasib alone or in combination with cetuximab to determine how many participants experience a cancer response.
Early-phase research includes NCT05067283, a phase 1 study with a substantial enrollment of 830 participants. This trial evaluates the safety, pharmacokinetics, and efficacy of Calderasib alone and in various combinations for advanced solid tumors with the KRAS G12C mutation.
Finally, NCT07219550 is a phase 1 study with 58 participants, including those with hepatic impairment and healthy volunteers. This study focuses on understanding how Calderasib levels change in the body over time in different populations.
Where to Participate
Clinical trials for Calderasib are being conducted across a wide geographic area, with studies active at 54 sites in 45 cities across 25 states. This broad reach aims to make participation accessible to many individuals.
Some of the locations with multiple participating sites include:
- Lancaster, Pennsylvania
- Hackensack, New Jersey
- Miami Beach, Florida
- Orlando, Florida
- Albany, New York
- Billings, Montana
- Fairfax, Virginia
- Baltimore, Maryland
- Grand Rapids, Michigan
- Stamford, Connecticut
Eligibility for these studies generally requires participants to be between 18 and 80 years of age. All genders are welcome to participate. Some studies also include healthy volunteers to help understand how Calderasib affects different body systems.
Development Timeline
The journey of Calderasib began with its first clinical trial on October 5, 2021, initiated by Merck Sharp & Dohme LLC. Since then, the development program has expanded significantly, with a total of 15 trials launched and an overall enrollment target of 3,722 participants.
Initially, research into Calderasib explored conditions such as IBS-C and hyperphosphatemia. However, the focus of the development pipeline quickly broadened. The program expanded to include studies in hepatic impairment and, notably, various forms of cancer, including neoplasm malignant, rectal adenocarcinoma, and advanced solid tumors. Later, colon adenocarcinoma and renal impairment were also added to the list of investigated conditions.
The development has progressed through different phases, with the majority of trials, 9 in total, being early-stage Phase 1 studies. This foundational work has paved the way for more advanced research, including 5 Phase 3 trials and 1 Phase 2 trial. The latest trial is projected to conclude by April 28, 2026, reflecting the ongoing commitment to understanding Calderasib's potential across its expanding indications.