According to a press release from PR Newswire and GuruFocus, drug discovery and development company Sutro Biopharma received promising phase 1 clinical data for their drug therapy STRO-002. Their Phase 1 clinical trial, which examines dose escalation for patients with ovarian cancer, found STRO-002 to be safe, effective, and well-tolerated. In addition, the drug therapy prevented tumor growth.

Ovarian Cancer

Ovarian cancer is a type of cancer that forms in the ovaries, part of the female reproductive system. Ovaries are almond-shaped organs where eggs are stored. Additionally, these organs produce estrogen and progesterone. A mutated BRCA gene is the culprit for BRCA-mutated ovarian cancer. A mutated BRCA gene is also the culprit for certain subsets of breast cancer. However, the cause of non-BRCA-mutated ovarian cancer is not clear.

There are four subsets of ovarian cancer:

• Forming 90% of diagnoses: epithelial tumors. In these cases, the cancer occurs in the tissue covering the ovaries.
• Forming 5% of diagnoses each: stromal carcinoma tumors and germ cell carcinoma tumors. In the former, cancer develops in ovarian connective tissue, the same tissue which produces hormones. In the latter, the cancer begins in the cells of the eggs.
• Forming 0.1% of diagnoses: small cell carcinoma of the ovary. This rare tumor is dangerous and highly malignant.

Ovarian cancer also occurs in four stages. In stage I, it remains in the ovaries. Stage II sees the cancer metastasizing to the pelvis, with stage III spreading to the abdomen. Finally, in stage IV, the ovarian cancer spread to other areas of the body, including the lungs, liver, and lymph nodes.

Symptoms of ovarian cancer include bloating, pelvic pain, changes in urination, abnormal uterine bleeding, breast tenderness, an enlarging abdomen, and menstrual irregularities. Learn more about ovarian cancer.

STRO-002

STRO-002 is a folate receptor alpha (FolRα) antibody-drug conjugate (ADC). Let’s break that down a little bit for clarity:

• Folate receptor alpha (FolRα): folate receptor alpha is a gene which encodes specific types of protein that bind folic acid. If FolRα is deficient, it can lead to neurodegeneration or poor fetal development. Folate, and folic acid, both play important roles in cell growth, development, and metabolism. However, if FolRα is over-expressed, it can lead to tumor and cancer development. In fact, an article in Clinical Gynecologic Oncology notes that FolRα is over-expressed in 90% of patients with ovarian cancer.
• Antibody-drug conjugate: antibody-drug conjugates are targeted drug therapies that bind to a specific antigen, or a foreign invader in the body. These ADCs have extreme anti-tumor properties and prompt cancerous cell death. In the case of STRO-002, the ADC works to inhibit excess FolRα.

This drug therapy was created by Sutro Biopharma, a Californian company looking to create oncological therapies for patients with unmet needs. They used XpressCF+™ cell-free protein synthesis technology, which is unique to their company. In addition to STRO-002, Sutro Biopharma created STRO-001 for patients with multiple myeloma and non-Hodgkin lymphoma. Moving forward, the company looks to create therapies that cause cancerous cell death while maintaining the health of non-cancerous cells.

Phase 1 Clinical Trial

The Phase 1 clinical trial (NCT03748186) enrolled 30 patients with ovarian cancer that was not responding well to other treatments. Most patients tried an average of 5 treatments prior to STRO-002. Researchers sought to understand the treatment’s effective dosage, safety, anti-tumor activity, tolerability, and potential adverse reactions. They found that:

• 75% of patients receiving 2.9 mpk of STRO-002 showed a partial response or stable disease state.
• 62% of patients reduced CA-125 levels by 50% or more, or normalized their CA-125 levels.
  • Cancer antigen 125 (CA-125) is a protein that can help monitor ovarian cancer. LabTestsOnline notes that CA-125 is elevated in 80% of ovarian cancer diagnoses. A reduction in CA-125 means that the cancer is responding to treatment.
• Some patients did experience adverse reactions. However, 89% of these were relatively mild. The other adverse reactions which required treatment were:
  • Fatigue
  • Myalgia (muscle pain)
  • Diarrhea
  • Arthralgia (joint pain)
  • Peripheral neuropathy
  • Neutropenia (low white blood cell count)

However, any patients presenting with neutropenia had their conditions reversed within one week. Moving forward, Sutro Biopharma looks to continue this trial with 5.2-6.0 mpk doses towards the end of 2020. As it stands, STRO-002 offers an effective and well-tolerated therapy for patients with ovarian cancer.