Acclaim-3

Combining Reqorsa® Gene Therapy with Tecentriq® (atezolizumab) in ES-SCLC

The Acclaim-3 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA, in combination with Genentech, Inc.’s Tecentriq® (atezolizumab) as maintenance therapy in patients with extensive stage small cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment.

In June 2023, the U.S. Food and Drug Administration granted Fast Track Designation for the Acclaim-3 treatment combination of REQORSA and Tecentriq as maintenance therapy in patients with ES-SCLC who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. In August 2023, the FDA granted Orphan Drug Designation to REQORSA for the treatment of SCLC.

The Phase 1 dose escalation portion of the Acclaim-1 trial has been completed.  Patients were treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. The primary endpoint of the Phase 1 escalation portion was to determine the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D). 

The Phase 2 expansion portion will enroll approximately 50 patients at approximately 10 to 15 U.S sites. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. The primary endpoint of the Phase 2 portion is to determine the 18-week progression-free survival rate from the time of the start of maintenance therapy with REQORSA and Tecentriq in patients with ES-SCLC. Patients will also be followed for survival. A Phase 2 futility analysis will be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up.

Phase 1 Dose Escalation

Although decreases in tumor size are not expected during maintenance therapy with atezolizumab alone, there were two patients out of the six enrolled in the Phase 1 dose escalation portion of the study who had marked decreases in measurable disease.

One patient had a partial remission, which is defined as at least a 30% decrease in tumor size, from prior to the start of maintenance therapy to the time of the CT scan performed after two cycles of maintenance therapy. A CT scan performed after four cycles of maintenance therapy (three months), confirmed that the patient still had a 30% decrease in tumor size in measurable lesions; however, one lesion not previously measurable had grown in size, thus leading to a conclusion of disease progression at that time.  

Another patient had a 23% decrease in tumor size from prior to the start of maintenance therapy to the time of the CT scan performed after two cycles of maintenance therapy. This patient received seven cycles of study therapy before progressing after 4.2 months. 

In addition, another patient achieved an unconfirmed partial remission after 24 cycles of therapy and continues to receive study treatment in the trial after more than 18 months.

Reqorsa® Adds Significantly to Tecentriq Treatment

Data presented at the October 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics from studies in humanized mouse models of SCLC that use human H841 cells have shown that the combination of REQORSA and Tecentriq (atezolizumab) provides significantly better control of tumor burden than either agent alone. 

H841 is a human SCLC cell line that does not express TUSC2 protein, and which was labeled with luciferase for these experiments. When injected intravenously, H841 cells metastasize to both lung and liver. The reconstituted humanized mice have a fully competent human immune system with major functional immune populations, which showed antigen specific T cell responses as well as antitumor activity with immune checkpoint blockade therapy and was used here to evaluate synergy between REQORSA and Tecentriq (atezolizumab).

In summary, the data from these studies suggest that a combination treatment of REQORSA +Tecentriq can promote a significantly increased tumor cell killing effect in SCLC xenografts compared to that of Tecentriq (atezolizumab) alone.