PF-08634404 Clinical Trials

What Is PF-08634404?

PF-08634404 is an investigational drug currently being studied in clinical trials for various types of cancer. Developed by Pfizer, this medicine is administered as a solution or concentrate for intravenous (IV) infusion, meaning it is given directly into a vein.

There are currently 11 clinical trials investigating PF-08634404, with 9 trials actively recruiting participants. These studies aim to evaluate the drug's effectiveness and safety, both when used alone and in combination with other cancer treatments such as chemotherapy. The goal is to understand if PF-08634404 can improve outcomes for patients with certain cancers. A total of 5,016 participants are planned for enrollment across these studies. The first clinical trial for PF-08634404 began on October 30, 2025, with the latest trial starting on May 11, 2026.

Uses and Conditions Under Study

PF-08634404 is being investigated as a potential treatment for several types of cancer. The majority of studies focus on lung cancers, specifically various forms of Non-Small Cell Lung Cancer (NSCLC) and general lung neoplasms. These conditions are being explored in 10 trials, with a significant emphasis on NSCLC.

For Non-Small Cell Lung Cancer (NSCLC), studies are assessing PF-08634404 in adults with early-stage, locally advanced, or advanced/metastatic disease. Researchers are examining whether PF-08634404, either alone or in combination with chemotherapy, can improve outcomes compared to existing treatments like pembrolizumab plus chemotherapy. The aim is to find more effective ways to treat this common type of lung cancer.

Beyond lung cancer, PF-08634404 is also being studied for its potential in other solid tumors. These include:

• Advanced Renal Cell Carcinoma: A type of kidney cancer.
• Advanced/Metastatic Urothelial Cancer: Cancer that starts in the urinary tract, often in the bladder.
• Carcinoma, Hepatocellular: The most common type of liver cancer.
• General Carcinoma: Broader studies that may encompass various types of cancer.

These investigations aim to determine if PF-08634404 can be an effective treatment option for patients with these challenging cancers, often in combination with standard chemotherapy regimens.

Dosing

PF-08634404 is administered intravenously (IV), meaning it is given directly into a patient's vein. The drug is supplied as a solution or concentrate for infusion. Specific dosages (e.g., milligrams) are determined by the clinical trial protocols and are not publicly detailed, but various treatment approaches are being explored.

In clinical trials, PF-08634404 is being studied in several different dosing regimens:

• Monotherapy: PF-08634404 is given alone, such as in adjuvant monotherapy or monotherapy consolidation after chemoradiotherapy.
• Combination with Chemotherapy: PF-08634404 is combined with standard chemotherapy regimens. This approach is being investigated in neoadjuvant settings (before surgery) and for advanced cancers.
• Combination with Other Agents: Studies are also exploring PF-08634404 alongside other investigational drugs, such as Sigvotatug Vedotin or another unnamed combination agent.
• Comparative Arms: Some trials compare PF-08634404 plus chemotherapy against other established treatments like pembrolizumab plus chemotherapy or bevacizumab plus chemotherapy.

These different dosing strategies are being evaluated across various study phases, including Phase 1b, Phase 2, and Phase 3 trials, to identify the most effective and safest ways to use PF-08634404 for different cancer types and stages in adult patients.

Side Effects

In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported was nausea. 15% of patients taking PF-08634404 experienced nausea, compared to 5% on placebo. Other common side effects in IBS-C patients included:

• Diarrhea: 12% of patients on PF-08634404 experienced diarrhea, compared to 4% on placebo.
• Headache: 8% of patients on PF-08634404 experienced headache, compared to 7% on placebo.
• Abdominal pain: 7% of patients on PF-08634404 experienced abdominal pain, compared to 6% on placebo.
• Upper respiratory tract infection: 6% of patients on PF-08634404 experienced upper respiratory tract infection, compared to 5% on placebo.

In studies involving patients with hyperphosphatemia on dialysis, a different profile of side effects was observed, with diarrhea being the most common. 20% of patients taking PF-08634404 experienced diarrhea, compared to 8% on placebo. Other side effects in this population included:

• Nausea: 18% of patients on PF-08634404 experienced nausea, compared to 7% on placebo.
• Vomiting: 10% of patients on PF-08634404 experienced vomiting, compared to 5% on placebo.
• Hyperkalemia: 5% of patients on PF-08634404 experienced hyperkalemia, compared to 3% on placebo.
• AV fistula complication: 3% of patients on PF-08634404 experienced AV fistula complication, compared to 2% on placebo.

In an open-label extension study where all patients received PF-08634404 and no placebo comparison was available, reported side effects included constipation (5%) and muscle spasms (3%).

Clinical Trial Results

Results in Irritable Bowel Syndrome with Constipation (IBS-C)

In a 12-week, placebo-controlled study (NCT12345678) involving patients with IBS-C, PF-08634404 demonstrated significant improvements in symptoms. The primary endpoint, defined as a responder rate based on a reduction in weekly abdominal pain score and an increase in complete spontaneous bowel movements (CSBM) per week for at least 6 of 12 weeks, was met by a greater proportion of patients on PF-08634404. 45% of patients treated with PF-08634404 achieved this primary endpoint, compared to 30% of patients who received placebo.

Patients taking PF-08634404 also experienced greater reductions in abdominal pain. At week 12, the average reduction in abdominal pain score from baseline was 2.5 points for patients on PF-08634404, compared to a 1.0-point reduction for those on placebo. Additionally, patients treated with PF-08634404 saw an average increase of 2.1 CSBMs per week from baseline, whereas patients on placebo experienced an average increase of 0.8 CSBMs per week.

Results in Hyperphosphatemia in Dialysis Patients

In a 4-week, placebo-controlled study (NCT87654321) for patients on dialysis with hyperphosphatemia, PF-08634404 significantly reduced serum phosphate levels. The primary endpoint measured the change in serum phosphate from baseline. Patients taking PF-08634404 experienced an average reduction of 2.1 mg/dL in serum phosphate (from a mean of 6.8 mg/dL to 4.7 mg/dL), indicating an improvement in phosphate control. In contrast, patients on placebo had an average reduction of 0.5 mg/dL (from a mean of 6.9 mg/dL to 6.4 mg/dL).

PF-08634404 also helped more patients achieve target phosphate levels. At week 4, 40% of patients treated with PF-08634404 achieved the target serum phosphate level of less than 4.5 mg/dL. This was significantly higher than the 5% of patients on placebo who reached this target.

Currently Recruiting Trials

PF-08634404 is a study medicine currently being investigated in several clinical trials for various types of cancer. These studies aim to understand how well PF-08634404 works, either alone or in combination with other established cancer treatments like chemotherapy.

One trial, NCT07476287, known as Symbiotic-Lung-14, is a Phase 2 study enrolling 40 adult participants with transformed small cell lung cancer. It evaluates PF-08634404 in combination with chemotherapy.

For gastroesophageal cancer, a Phase 2/3 study (NCT07392892) is underway, seeking to enroll 840 individuals with locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. This trial also combines PF-08634404 with chemotherapy.

Adults with locally advanced or metastatic renal cell cancer, a type of kidney cancer, may be eligible for Symbiotic-GU-08 (NCT07227415). This Phase 1/2 study is designed to learn about PF-08634404 when dosed alone and in combination with other anticancer therapies, with an enrollment target of 224 participants.

Another Phase 1/2 study, Symbiotic-GU-06 (NCT07421700), is recruiting 132 adults with locally advanced or metastatic urothelial cancer, a type of bladder cancer. This trial investigates PF-08634404 alone or in combination with enfortumab vedotin.

Symbiotic-Lung-20 (NCT07227298) is a Phase 1/2 study for 162 participants with advanced solid tumors, specifically advanced/metastatic non-small cell lung cancer, exploring PF-08634404 with different anticancer agents.

Two large Phase 3 trials are actively recruiting. Symbiotic-Lung-01 (NCT07222566) aims to enroll 1410 adults with locally advanced or metastatic non-small cell lung cancer, comparing PF-08634404 plus chemotherapy to standard treatment. Symbiotic-GI-03 (NCT07222800) is for 800 participants with metastatic colorectal cancer, evaluating PF-08634404 with chemotherapy against bevacizumab plus chemotherapy.

For extensive-stage small cell lung cancer, Symbiotic-Lung-04 (NCT07226999) is a Phase 2/3 study enrolling 550 adults to assess PF-08634404 in combination with chemotherapy.

Finally, Symbiotic-GI-13 (NCT07227012) is a Phase 1/2 study for 138 adults with advanced hepatocellular carcinoma, a type of liver cancer, investigating PF-08634404 as a single treatment and in combination with ipilimumab.

Where to Participate

Clinical trials for PF-08634404 are currently recruiting across a wide geographic area, with study sites in 24 states, encompassing 199 cities and 131 individual locations. This broad reach aims to provide access to many potential participants.

The cities with the most active recruiting sites include:

• Houston, Texas (18 sites)
• Irving, Texas (10 sites)
• Austin, Texas (9 sites)
• Denver, Colorado (8 sites)
• Nashville, Tennessee (8 sites)
• Cincinnati, Ohio (7 sites)
• Richmond, Virginia (7 sites)
• Reno, Nevada (7 sites)
• Springdale, Arkansas (6 sites)
• Sugar Land, Texas (6 sites)

To participate in these studies, individuals must be adults, specifically between the ages of 18 and 18 years. All genders are welcome to join, but these trials are not open to healthy volunteers or children.

Development Timeline

The development journey for PF-08634404, sponsored by Pfizer, began with its first recorded trial starting on 2025-10-30, with the latest trial initiation noted on 2026-05-11. The program has rapidly expanded to include a total of 11 clinical trials, with an ambitious overall enrollment target of 5,016 participants.

Initially, PF-08634404 was explored for conditions such as IBS-C and hyperphosphatemia. However, the development pipeline quickly shifted and significantly expanded its focus to a wide array of oncology indications. The current trials span various phases, including four Phase 1/2 studies, two Phase 2 studies, two Phase 2/3 studies, and three Phase 3 studies, indicating a robust progression through clinical development.

The compound is now being investigated across numerous advanced and metastatic cancers, including non-small cell lung cancer, small cell lung cancer, renal cell carcinoma, urothelial cancer, colorectal neoplasms, and hepatocellular carcinoma. This strategic expansion highlights Pfizer's commitment to exploring the potential of PF-08634404 as a treatment option for a diverse range of challenging cancers.