Two clinical trials for solid tumor cancers take different approaches to stop growth

Friday, November 22, 2024

This month, we’re featuring two studies designed for people with solid tumors that are difficult to treat.

Both important studies are enrolling patients at Providence Cancer Institute of Oregon. The principal investigator is Rachel Sanborn, M.D., medical director of the Providence Thoracic Oncology Program and the Phase I Clinical Trials Program at Providence Cancer Institute.

Read on to learn about these studies, and to find other clinical trials currently enrolling patients.

Targeting SMARCA2 to slow or stop cancer from growing

A first-in-human study is underway to investigate PRT3789 as a therapy for people with cancer that has spread to other parts of the body despite treatment. Study participants must have cancers with an abnormal form of a gene called SMARCA4. When SMARCA4 doesn’t work well, tumors rely on another gene called SMARCA2 for growth. The therapy being evaluated in this study targets SMARCA2. Researchers hope that targeting SMARCA2 may slow or stop cancer growth.

This open-label, Phase I study, conducted across multiple centers, will evaluate the safety, tolerability pharmacokinetics (how the drug moves in the body), pharmacodynamics (how the drug affects the body) and potential tumor-fighting activity of PRT3789. Researchers are testing it as a monotherapy (alone) and in combination with docetaxel, a common chemotherapy drug.

Approximately 186 participants will be enrolled in study arms that include:

Monotherapy (PRT3789 only), which tests increasing doses of the drug
Backfill (Additional groups of study participants are enrolled in lower dose levels after a group has completed the safety evaluation period.)
The combination of PRT3789 with docetaxel chemotherapy

Learn more about this study: A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3789 in Participants With Select Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation

Can valemetostat synergize with DXd ADCs to treat solid tumor cancers?

This global study explores a new treatment approach for people with HER2-positive gastric cancer, non-squamous non-small cell lung cancer (NSCLC), or HER2-low breast cancer. The treatment approach combines valemetostat with different antibody-drug conjugates (DXd ADCs).

Why is the study important?

As a Phase Ib clinical trial, this study will assess the safety and optimal dose of therapy combinations to determine how well patients tolerate them and how they affect tumor growth. If the outcomes are positive, this approach may help people who have exhausted other treatment options.

The two-part design includes:

Part 1 (Dose-Escalation Phase): This first phase aims to find the optimal dose of valemetostat that can be safely combined with the ADCs. Participants in this phase receive gradually increasing doses of the drug until the most suitable dose for further testing is established.
Part 2 (Dose-Expansion Phase): In the second phase, study participants receive the optimal dose of valemetostat (from Part 1) combined with a DXd ADC. This phase aims to monitor the safety of the combined treatment in a broader group of patients with HER2-positive and HER2-low cancers.

The study includes three sub-protocols for specific cancer types:

Sub-protocol A: Tests valemetostat with trastuzumab deruxtecan (T-DXd) in patients with previously treated unresectable or metastatic HER2-low IHC 1+ or IHC 2+/ISH-negative breast cancer.

Sub-protocol B: Combines valemetostat with T-DXd in patients with previously treated, advanced HER2-positive gastric or gastro-esophageal junction cancer.

Sub-protocol C: Investigates valemetostat with datopotamab deruxtecan (Dato-DXd) in patients with advanced or metastatic non-squamous NSCLC (with or without actionable genomic alterations).