Sarah Cannon Research Institute Experts Pinpoint Open Clinical Trials in Tennessee

Melissa Johnson, MD

Spanning metastatic non–small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and HER2-low breast cancer, here are 4 must-know clinical trials in Tennessee that community oncologists can now enroll their patients on.

Advanced NSCLC

The multi-center, open-label, phase 2 (NCT04681131) and phase 1/2 (NCT03504488) trials will assess the safety, tolerability, immunogenicity, pharmacokinetic (PK) and antitumor activity of BA3011 and BA3021, conditionally active biologic AXL- and ROR2-targeted targeted antibody-drug conjugates, respectively, alone and in combination with a PD-1 inhibitor in patients with metastatic NSCLC and disease progression on a PD-1/PDL-1 inhibitor and advanced solid tumors/patients with melanoma and NSCLC, respectively.

Both trials are currently recruiting patients to their research site in Nashville, Tennessee.

The phase 2 study was launched on March 17, 2021 and has an estimated enrollment of 240 patients and an estimated completion date of December 2022.

Objective response rate (ORR) and incidence of adverse effects (AEs) or serious AEs will serve as the coprimary end points of the phase 2 study.

The phase 1/2 study was launched on June 27, 2018 and has an estimated enrollment of 420 patients and an estimated completion date of June 30, 2023.

The evaluation of dose-limiting toxicity (DLT), maximum-tolerated dose, frequency and severity of AEs and/or serious AEs, and confirmed ORR will serve as the primary end points of the phase 1/2 study.

“These are sister studies from BioAtla using their ADC [antibody-drug conjugate] platform. The study design is the same for both [trials]. The [phase 2] trial [is evaluating an ADC that] targets AXL while the [phase 1/2] study [is evaluating an ADC that] targets ROR2. Patients can go through prescreening for both [targets] at the same time,” said Melissa Johnson, MD, program director of lung cancer research at Sarah Cannon Research Institute.

“Patients with NSCLC are expected to be positive for AXL approximately 30% of the time and positive for ROR2 approximately 30% of the time, and very rarely would be positive for both. These are good, targeted therapy options for patients who otherwise would receive docetaxel,” added Johnson.

Metastatic CRPC

This phase 1/2 dose-escalation trial (NCT03888612) will evaluate the safety and tolerability of ARV-110 in men with metastatic CRPC who have progressed on prior approved systemic therapies for castration-resistant disease, 1 of which must be enzalutamide (Xtandi) or abiraterone acetate (Zytiga).

In parts A and B, oral tablets of ARV-110 will be given once or twice daily in 28-day cycles. In part A, daily oral dosing will be predetermined by a cohort review committee after the initial starting dose cohort following the first 28 days of treatment. In part B, daily oral dosing will be given at the recommended phase 2 dose.

The primary end points of part A of the study include the incidence of DLTs, the number of patients with AEs, and the incidence of laboratory abnormalities. In part B, primary objectives include the measurement of prostate-specific antigen response, the measurement of overall RECIST response rate, and the clinical antitumor activity of ARV-110.

Research sites for the study, all currently recruiting, include Dickson, Franklin, Gallatin, Hendersonville, Hermitage, Lebanon, Murfreesboro, Nashville, Shelbyville, and Smyrna, Tennessee.

The phase 1/2 study was launched on March 1, 2019 and has an estimated enrollment of 150 patients and an estimated completion date of April 30, 2023.

“The androgen receptor is the key driver of CRPC during the transition from localized to metastatic disease, with AR [androgen receptor] gene aberrations, encompassing amplifications and mutations, occurring in 60% to 85% of patients,” said Benjamin Garmezy, MD, an investigator, and Meredith McKean, MD, MPH, associate director of Melanoma and Skin Cancer Research, both at Sarah Cannon Research Institute.

“This study from Arvinas features a novel AR degrader as treatment for patients with previously treated metastatic CRPC. Initial efficacy data has shown a promising response in patients with specific AR mutations,” added Garmezy and McKean.

HER2-Low Advanced or Metastatic Breast Cancer

The phase 1b DESTINY-Breast08 trial (NCT04556773) will evaluate the safety, tolerability, PK, and preliminary antitumor activity of fam-trastuzumab deruxtecan-nxki (Enhertu) in combination with other therapies in patients with metastatic HER2-low advanced or metastatic breast cancer.

HER2 low will be defined as immunohistochemistry (IHC) 1+ or IHC 2+/ISH-. Part 1 of each module will enroll patients with locally confirmed HER2-low advanced or metastatic breast cancer in need of second or later-line treatment.

Part 2 of each module will enroll patients with HER2-low metastatic breast cancer who have not received prior treatment, or received only 1 prior treatment for advanced or metastatic disease.

The study will consist of 5 cohorts. Each module will have 2 parts: a dose-finding phase (part 1) and a dose-expansion phase (part 2). The part 2 dose-expansion phase will use the recommended phase 2 dose for the combination, either as determined in part 1 or from another clinical study if appropriate.

In each cohort, patients will receive:

• Cohort 1: 5.4 mg/kg of intravenous (IV) trastuzumab deruxtecan every 3 weeks plus 1000 mg/m² of oral capecitabine twice daily on days 1 through 14 every 3 weeks
• Cohort 2: 5.4 mg/kg of IV trastuzumab deruxtecan every 3 weeks plus 1120 mg of IV durvalumab (Imfinzi) every 3 weeks plus 80 mg/m² of IV paclitaxel every 3 weeks
• Cohort 3: 5.4 mg/kg of IV trastuzumab deruxtecan every 3 weeks plus 400 mg of oral capivasertib twice daily
• Cohort 4: 5.4 mg/kg of IV trastuzumab deruxtecan every 3 weeks plus 1 mg of oral anastrozole daily
• Cohort 5: 5.4 mg/kg of IV trastuzumab deruxtecan every 3 weeks plus 500 mg of intramuscular fulvestrant (Faslodex) every 4 weeks

The primary end points include the occurrence of AEs and serious AEs in parts 1 and 2.

Research sites for the study, all currently recruiting, include Dickson, Franklin, Gallatin, Hendersonville, Hermitage, Lebanon, Murfreesboro, Nashville, Shelbyville, and Smyrna in Tennessee.

The phase 1 study was launched on December 17, 2020 and has an estimated enrollment of 185 patients and an estimated completion date of August 28, 2023.

“From the patient perspective, the HER2-low subgroup is considered HER2 negative, and hence are told they are ineligible for HER2-targeted therapies. However, patients with HER2-low disease can derive benefit from treatment with this potent HER2-targeted ADC––trastuzumab deruxtecan––due to its demonstrated efficacy in a phase 1 trial in this subset of patients,” said Erika Hamilton, MD, director of the Breast Cancer and Gynecologic Cancer Research Program and principal investigator at Sarah Cannon Research Institute.

Hepatocellular Carcinoma

The phase 3 IMbrave050 trial (NCT04102098) will evaluate the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) vs active surveillance as adjuvant therapy in patients with completely resected or ablated hepatocellular carcinoma who are at high risk of recurrence.

Patients randomized to the combination will receive 1200 mg of IV atezolizumab on day 1 of each 21-day cycle plus 15 mg/kg of IV bevacizumab on day 1 of each 21-day cycle until disease recurrence or unacceptable toxicity.

The primary end point is recurrence-free survival.

The trial is currently recruiting patients to their research site in Nashville, Tennessee.

The phase 3 study was launched on December 31, 2019 and has an estimated enrollment of 662 and an estimated completion date of July 16, 2027.

“It has been challenging to catch patients after surgical resection who are at a high risk of recurrence to enroll on trial. The combination of atezolizumab and bevacizumab is active in the metastatic first-line setting and is now standard of care. This trial seeks to investigate the benefit of this combination for patients in the adjuvant setting,” said Meredith Pelster, MD, MSCI, a medical oncologist and clinical investigator at Sarah Cannon Research Institute.

For all studies, please contact DDUreferrals@sarahcannon.com for any study or patient enrollment inquiries.