Apalutamide Clinical Trials

What Is Apalutamide?

Apalutamide is an FDA-approved medication for metastatic hormone-sensitive prostate cancer (mHSPC). This type of prostate cancer has spread to other parts of the body but still responds to treatments that lower male hormone levels. Apalutamide works as an androgen receptor pathway inhibitor, which means it blocks the signals from male hormones (androgens) that can promote the growth of prostate cancer cells. By inhibiting these receptors, Apalutamide helps to slow the disease's progression.

Beyond its approved use, Apalutamide is also being investigated in numerous clinical trials for other types of prostate cancer. These include non-metastatic prostate cancer (nmPC), recurrent prostate cancer, and advanced cancers with specific genetic mutations. Some studies are exploring its use in combination with other approved agents for prostate cancer, such as androgen deprivation therapy (ADT), or with investigational drugs to assess safety and effectiveness. Apalutamide is considered an investigational drug in some of these specific research contexts.

Uses and Conditions Under Study

Apalutamide is primarily studied for various forms of prostate cancer, a common non-skin cancer among men. It functions as an androgen receptor pathway inhibitor, aiming to disrupt the growth of cancer cells that rely on male hormones.

• General Prostate Cancer: Apalutamide is being investigated in a broad range of prostate cancer conditions, including general Prostate Cancer (35 trials), Prostatic Neoplasms (15 trials), and Prostate Adenocarcinoma (11 trials). These studies aim to understand its efficacy across different presentations of the disease.
• Metastatic Prostate Cancer: A significant focus of research is on metastatic forms, where cancer has spread beyond the prostate. This includes Metastatic Prostate Cancer (6 trials), Metastatic Prostate Carcinoma (5 trials), and metastatic hormone-sensitive prostate cancer, which is also an FDA-approved indication for Apalutamide. Studies explore how Apalutamide can help manage the disease in these advanced stages, often in combination with other therapies like androgen deprivation therapy (ADT).
• Specific Stages of Prostate Cancer: Clinical trials also examine Apalutamide's role in specific stages of prostate cancer, as defined by the AJCC staging system. This includes advanced stages such as Stage IVB Prostate Cancer AJCC v8 (7 trials), Stage IVA Prostate Cancer AJCC v8 (6 trials), Stage IV Prostate Cancer AJCC v8 (4 trials), and Stage IV Prostate Adenocarcinoma AJCC v7 (4 trials). Additionally, it is being studied in Stage IIIA Prostate Cancer AJCC v8 (3 trials). These trials investigate whether Apalutamide can improve outcomes for patients at particular points in their disease progression.

In total, Apalutamide has been studied in 110 trials involving 52,849 participants since the first trial began in 2013. Currently, 26 trials are recruiting new participants, while 31 trials have been completed.

Dosing

Apalutamide is available in tablet form for oral administration. The recommended daily dose, as outlined in the Summary of Product Characteristics (SmPC), is 240 mg. This dose can be achieved by taking four 60 mg tablets or a single 240 mg tablet once daily.

In clinical trials, Apalutamide has been studied in various dosing regimens and combinations for prostate cancer. These include:

• Apalutamide monotherapy, where it is given alone.
• Combination therapy with androgen deprivation therapy (ADT), which is a common approach for prostate cancer treatment.
• Combinations with other agents such as docetaxel, abiraterone acetate, prednisone, or investigational drugs like relugolix or AZD5305.
• Studies have also explored its use alongside local treatments like radiotherapy (SBRT) or surgery.

Different study arms have investigated Apalutamide in various contexts, including intermittent versus continuous ADT, neoadjuvant (before surgery) or adjuvant (after surgery) settings, and in patients with severe hepatic impairment to assess dose adjustments. The specific treatment plan is determined by the healthcare provider based on the patient's condition and the clinical practice guidelines.

Side Effects

In clinical trials involving patients with prostate cancer, the most common side effect reported with Apalutamide was fatigue. Approximately 26.9% of patients taking Apalutamide experienced fatigue, compared to 19.2% of patients on placebo. These side effects were observed in studies involving a total of 1939 patients treated with Apalutamide across multiple trials. Other common side effects included:

• High blood pressure (hypertension), reported by 24.1% of patients on Apalutamide versus 18.0% on placebo.
• Joint pain (arthralgia), affecting 18.7% of patients on Apalutamide compared to 14.9% on placebo.
• Decreased weight, observed in 17.0% of patients taking Apalutamide versus 8.9% on placebo.
• Hot flashes, occurring in 17.0% of patients on Apalutamide compared to 11.1% on placebo.
• Diarrhea, reported by 16.1% of patients on Apalutamide versus 10.7% on placebo.
• Falls, experienced by 15.1% of patients on Apalutamide compared to 10.5% on placebo.
• Rash, which affected 13.9% of patients on Apalutamide compared to 5.6% on placebo.

Other reported side effects, with similar rates between Apalutamide and placebo, included back pain (18.9% vs 18.6%), nausea (14.9% vs 12.0%), constipation (13.3% vs 12.9%), and pain in extremities (11.8% vs 9.2%).

Clinical Trial Results

Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)

In a study (NCT01946204) of men with non-metastatic castration-resistant prostate cancer, treatment with Apalutamide significantly extended the time until metastasis or death. Patients receiving Apalutamide had a median metastasis-free survival of 40.51 months, compared to 15.70 months for those on placebo. Similarly, the median progression-free survival was 40.51 months with Apalutamide versus 14.72 months with placebo. The median time to metastasis was also longer for Apalutamide patients at 40.51 months, compared to 15.70 months for placebo.

Metastatic Castration-Resistant Prostate Cancer (mCRPC)

A clinical trial (NCT02257736) investigated Apalutamide in combination with abiraterone acetate and prednisone for patients with chemotherapy-naive metastatic castration-resistant prostate cancer. The combination therapy with Apalutamide resulted in a median radiographic progression-free survival of 23.98 months, compared to 16.59 months for patients receiving placebo alongside abiraterone acetate and prednisone. Overall survival was also slightly longer in the Apalutamide combination group, with a median of 36.17 months compared to 33.71 months for the placebo combination. However, the median time to chronic opioid use and time to pain progression were shorter in the Apalutamide combination group compared to the placebo combination group.

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

In a study (NCT02489318) evaluating Apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in participants with metastatic hormone-sensitive prostate cancer, the median overall survival and radiographic progression-free survival for the Apalutamide + ADT group were not reached at the time of analysis. This suggests a prolonged benefit compared to the placebo + ADT group, which had a median overall survival of 52.17 months and a median radiographic progression-free survival of 22.08 months.

Prostate Cancer on Active Surveillance

For patients with prostate cancer undergoing active surveillance, a study (NCT02721979) reported that patients treated with Apalutamide had a median local treatment-free survival of 874 days. Additionally, 59% of subjects had a negative biopsy (no residual carcinoma) after treatment. The percentage of patients exiting active surveillance due to pathologic reclassification was 18.2%, and 22.7% exited for any reason. The median prostate-specific antigen progression-free survival was 365 days.

Currently Recruiting Trials

Where to Participate

• St Louis, Missouri (19 sites)
• New York, New York (16 sites)
• Seattle, Washington (15 sites)
• Pittsburgh, Pennsylvania (14 sites)
• Anchorage, Alaska (13 sites)
• Los Angeles, California (13 sites)
• Las Vegas, Nevada (12 sites)
• Philadelphia, Pennsylvania (12 sites)
• Honolulu, Hawaii (12 sites)
• Chicago, Illinois (12 sites)

Development Timeline