Three phases of clinical trials round out a year of research advancements

December 6, 2022

Earle A. Chiles Research Institute

In the past year Providence Cancer Institute has opened dozens of clinical trials, each one an effort to advance cancer treatment for patients around the globe. At any given time, we have over 400 clinical trials in progress, including ones initiated by our own researchers. These include early phase studies that test medications in people for the first time, as well as phase III and IV trials, which study new medications or treatments in comparison to standard treatments.

This month we wrap up a highly productive and remarkable year in research by featuring a phase III trial for patients with gynecologic cancers and two early phase trials that will study new medications in treating solid tumors.

Randomized study will evaluate a combination of therapies in patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancers

This phase III study, known as ARTISTRY-7, will evaluate randomized therapeutic approaches in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (a rare type of cancer that forms on the lining of the abdomen and pelvis).

Platinum-resistant ovarian cancer refers to cancer that progresses within six months of chemotherapy. An effective treatment remains elusive, however, the therapies to be evaluated in ARTISTRY-7 have demonstrated encouraging clinical activity in an early trial.

Four experimental arms

Participants in ARTISTRY-7 will randomly receive either nemvaleukin alfa alone, nemvaleukin alfa in combination with pembrolizumab, pembrolizumab alone, or an investigator’s choice of a chemotherapy that includes one of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan or gemcitabine.

In 2021, the FDA granted fast-track designation to nemvaleukin alfa, an engineered immunotherapy, plus pembrolizumab for patients with platinum-resistant ovarian cancer. According to the FDA, “the designation was intended to “facilitate the development of the combination [nemvaleukin alfa plus pembrolizumab] and accelerate review.”

The FDA’s fast-track designation followed findings from the phase I/II study (ARTISTRY-1) of nemvaleukin alfa plus pembrolizumab. Within a cohort of 14 patients with platinum-resistant ovarian cancer, one patient achieved a complete response, three achieved partial responses and six had stable disease. The data from ARISTRY-1 was presented in March at the SGO 2022 Annual Meeting on Women’s Cancer.

Now recruiting

The Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, is currently recruiting patients for ARTISTRY-7. Christopher Darus, M.D., MS, medical director, Providence Gynecologic Oncology Program, is the principal investigator.

Learn more about the study here:

Nemvaleukin Alfa in combination with pembrolizumab versus investigator’s choice chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer

Assessing the safety, tolerability and efficacy of EP0031 in patients with advanced RET-altered cancers

A new clinical trial for people with RET-altered cancers is currently open at the Earle A. Chiles Research Institute. This phase I/II study will assess EP0031 (A400), a potent and targeted inhibitor against RET-driven cancers. RET alterations account for 2% of all cancers, particularly in non-small cell lung, thyroid, ovarian, breast, pancreatic and colorectal cancers.

RET-altered cancers are caused by a mutation or abnormal re-arrangement of the RET gene that in turn switches the cell membrane receptor to the “on” position, where it remains. The result is abnormal cells multiplying and spreading, driving cancer growth.

Progressive treatment with new SRI

Initially, RET-altered cancers were treated with multikinase inhibitors which had modest efficacy with notable side effects. More recently, selective RET-inhibitors (SRI) selpercatinib and pralsetinib demonstrated clinical benefit, but within 1-3 years patients become resistant to the therapies.

EP0031 is a next generation SRI designed to address some of the issues of first-generation therapies. In June 2022, the FDA cleared the investigational new drug (IND) application for EP0031.

IND approval of EP0031 paved the way for the phase I/II trial presented here, which will evaluate dose escalation and dose expansion of EP0031 in patients with advanced RET-altered cancers, including patients with no prior SRI therapy. Currently, there are no approved RET-targeted treatments for patients who progress on first-generation SRIs.

Multiple arm study

In this trial, researchers will evaluate EP0031 in six experimental arms based on tumor type: fusion-positive non-small cell lung cancer, mutation-positive medullary thyroid cancer and RET-altered solid tumors. Patients will be assigned to a prior SRI therapy arm, or a no prior SRI therapy arm.

Matthew Taylor, M.D., medical director, Providence Thyroid Cancer Program, co-medical director, Providence Melanoma Program, is principal investigator of the study. Dr. Taylor also leads the Developmental Cancer Therapeutics Laboratory at Earle A. Chiles Research Institute.

Learn more about the trial:

A study of EP0031-101 in patients with advanced RET-altered malignancies

Study assesses safety and efficacy of BA3071 in solid tumors

In this phase I/II trial, BA3071, a new CTLA-4 inhibitor, will be evaluated in combination with nivolumab, a PD-1 blocking antibody, in patients with a range of advanced solid tumors. BA3071 was developed using conditionally active biologic (CAB), a proprietary technology, based on the creation of compounds that can be activated or inactivated under specific conditions. BA3071 becomes active and blocks the CTLA-4 receptor on the surface of T cells when it reaches the tumor. Downregulating the signal to T cells helps boost the body’s immune response against cancer cells.

Nivolumab is a type of immunotherapy and works as a checkpoint inhibitor. Nivolumab blocks a signal that prevents activation of T cells and in combination with other checkpoint inhibitors has led to new immunotherapies for different types of cancer, including melanoma and non-small cell lung cancer.

In this study, researchers will assess the safety and efficacy of BA3071 combined with nivolumab to determine its progression to a phase III trial.

Providence Cancer Institute is the only site in Oregon offering the trial. Matthew Taylor , M.D., medical director, Providence Thyroid Cancer Program, co-medical director, Providence Melanoma Program, is principal investigator. Dr. Taylor also leads the Developmental Cancer Therapeutics Laboratory at Earle A. Chiles Research Institute.