Phase 2 Trial Initiaties DS-7300 Treatment in ES-SCLC

Following positive phase 1/2 results of DS-7300 use in patients with extensive-stage small cell lung cancer, a phase 2 study has dosed its first patient with the experimental agent.

The first patient has been dosed in a global phase 2 trial (NCT05280470) evaluating the efficacy and safety of DS-7300 in patients with pretreated extensive-stage small cell lung cancer (ES-SCLC), according to Daiichi Sankyo.1

DS-7300 is a specifically designed, potential first-in-class B7-H3 directed antibody drug conjugate (ADC) currently being developed for the use in this patient population.

The phase 2 trial follows the positive data currently being evaluated in the phase 1/2 trial of DS-7300 in 3 patients with metastatic squamous non-small cell lung cancer, esophageal squamous cell carcinoma, or castration-resistant prostate cancer (NCT04145622). Findings have demonstrated DS-7300 to be tolerated across all dose levels, which ranged between 0.8 mg/kg and 16.0 mg/kg. Further, no dose-limiting toxicities were observed in the 70 patients enrolled. 2,3

“Patients with pretreated extensive-stage small cell lung cancer have limited treatment options following disease progression,” said Gilles Gallant, BPharm, PhD, FOPQ, senior vice president, global head, Oncology Clinical Development, oncology R&D of Daiichi Sankyo, in the press release. “Based on the encouraging results seen in the ongoing phase 1/2 trial, we have initiated this phase 2 trial of DS-7300 to further evaluate whether targeting B7-H3 with our DXd antibody drug conjugate technology may become a potential treatment option for patients with extensive-stage small cell lung cancer.”

Within the phase 2 trial, investigators will evaluate the efficacy and safety of 2 doses of DS-7300 in approximately 80 patients with histologically or cytologically confirmed ES-SCLC who have received at least 1 prior line of platinum-based chemotherapy. Patients will be randomized 1:1 to receive either an 8 mg/kg or 12 mg/kg dose of DS-7300.4

Enrollment in the trial is open to patients aged 18 years and older with histologically or cytologically documented ES-SCLC. Patients must have at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator, have had prior therapy with at least 1 platinum-based line as systemic therapy for extensive-stage disease, documentation of radiological disease progression on or after most recent systemic therapy, and an ECOG performance status of 0 or 1.

The trial’s primary end point is objective response rate (ORR) as assessed by blinded independent central review, with secondary end points including progression-free survival, duration of response, overall survival, time to response, disease control rate, investigator-assessed ORR, pharmacokinetics, immunogenicity, and safety. Further, the study aims to find the recommended phase 2 dose of DS-7300.

The trial is actively recruiting patients in Asia, Europe, and North America, and aims to be completed in November 2024.

In addition to the phase 2 trial examining DS-7300 in patients with ES-SCLC, the B7-H3 ADC is also being evaluated in a phase 1/2 trial examining 3 cohorts of patients with advanced solid tumors. Patients being examined have either metastatic squamous non-small cell lung cancer, esophageal squamous cell carcinoma, or castration-resistant prostate cancer.

This multicenter, first-in-human study is examining patients with advanced solid tumors who have not been cured by other treatments. The 2 parts of the trial include a dose-escalation portion to evaluate the safety and tolerability of DS-7300 and to determine the maximum tolerated dose and recommended dose for the expansion portion of the trial. In part 2, the dose-expansion part, the goal is to investigate the safety, tolerability, and antitumor activity of DS-7300 when administered as a single agent.

In this trial, DS-7300 was shown to be well tolerated across all dose levels and there were no dose-limiting toxicities observed in any of the enrolled patients.

In regard to safety, the most common treatment emergent adverse events (TEAEs) observed included nausea (55.7%), infusion-related reaction (40.0%), decreased appetite (28.6%), vomiting (27.1%), fatigue (21.0%), chills (12.9%), pyrexia (12.9%), dehydration (11.4%) and diarrhea (11.4%). Additionally, grade 3 or higher TEAEs regardless of causality were seen in 31.4% of patients (n = 22). The most common grade 3 or higher TEAEs included anemia (15.7%) and lymphocyte count decreased (2.8%).

Further, 1 patient who had been given the 16.0 mg/kg dose had interstitial lung disease (ILD) that developed and was associated with death. At the 12.0 mg/kg dose, there was 1 case of grade 1 ILD that was pending adjudication as of data cut-off of July 21, 2021. Since then, it has been adjudicated as treatment related.

Findings also showed that there were 15 partial responses (PR), including 10 confirmed PRs and 5 PRs awaiting confirmation, in patients with a range of solid tumors. In an additional 32 patients, including 24 patients who continue to be treated with various doses of DS-7300, stable disease has also been reported as of the data cut-off of July 21, 2021. Those enrolled in this dose escalation study received a median of 4 prior lines of therapy (range, 1-10).

“These initial safety and efficacy results of DS-7300 are encouraging as we observed that most patients in the study experienced some level of tumor shrinkage,” said Melissa Johnson, MD, director of the Lung Cancer Research Program at Sarah Cannon Research Institute, in a press release. “Based on these results, we are moving forward with the dose expansion part of the study where we are enrolling patients with metastatic small cell lung cancer, esophageal squamous cell cancer and castration-resistant prostate cancer to further evaluate the potential role of DS-7300 in these cancers.”

References:
  1. DS-7300 phase 2 trial initiated in patients with pretreated extensive-stage small cell lung cancer. News release. Daiichi Sankyo. July 20, 2022. Accessed July 26, 2022.https://bwnews.pr/3BcA2T5
  2. Study of DS-7300a in participants with advanced solid malignant tumors. ClinicalTrials.gov. Updated July 15, 2022. Accessed July 26, 2022. https://clinicaltrials.gov/ct2/show/NCT04145622?term=DS-7300&draw=2&rank=2
  3. Johnson ML, Doi T, Piha-Paul SA, et al. A phase I/II multicenter, first-in-human study of DS-7300 (B7-H3 DXd-ADC) in patients (pts) with advanced solid tumors. Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021; virtual. Abstract 513O.
  4. DS-7300a in subjects with pretreated extensive-stage small cell lung cancer (ES-SCLC). ClinicalTrials.gov. Updated June 30, 2022. Accessed July 26, 2022. https://clinicaltrials.gov/ct2/show/NCT05280470