HTMC0435 Plus Chemotherapy Yields Responses in Relapsed ES-SCLC

Fact checked by" Russ Conroy
News
Article

HTMC0435 plus temozolomide led to an ORR of 24.5%, with a median OS of 12.0 months, in patients with platinum-sensitive and platinum-resistant small cell lung cancer.

HTMC0435 plus temozolomide led to an ORR of 24.5%, with a median OS of 12.0 months, in patients with platinum-sensitive and platinum-resistant small cell lung cancer.

HTMC0435 plus temozolomide led to an ORR of 24.5%, with a median OS of 12.0 months, in patients with platinum-sensitive and platinum-resistant small cell lung cancer.

Combining the oral PARP inhibitor HTMC0435 with temozolomide (Temodar) led to promising antitumor activity and a manageable safety profile in patients with platinum-sensitive and platinum-resistant extensive-stage small cell lung cancer (ES-SCLC), according to results from a phase 1b/2 trial (NCT05728619) shared at the 2025 American Society of Clinical Oncology Annual Meeting.1

As of October 31, 2024, with a median follow-up of 10.3 months among all evaluable patients (n = 49), the objective response rate (ORR) was 24.5% (95% CI, 12.0%-37.0%) and the disease control rate (DCR) was 63.3% (95% CI, 49.3%-77.3%). There were 12 confirmed and 7 unconfirmed partial responses (PRs); of the 19 patients with PRs, 3 were still undergoing treatment. The median duration of response (DOR) was 6.9 months (95% CI, 1.22-12.58).

The median progression-free survival (PFS) was 2.8 months (95% CI, 1.16-4.44), and the median overall survival (OS) was 12.0 months (95% CI, 7.85-14.75).

In patients without brain metastases (n = 26), the ORR was 38.5% (95% CI, 20.2%-59.4%) and the DCR was 61.5% (95% CI, 40.6%-79.8%); the median DOR was 5.5 months (95% CI, 3.65-not calculable [NC]). The median PFS was 2.7 months (95% CI, 1.41-5.52), and the median OS was 12.0 months (95% CI, 8.11-NC).

In patients with platinum-resistant disease (n = 23), defined as a chemotherapy-free interval of less than 90 days, the ORR was 25.0% (95% CI, 8.7%-49.1%) and the DCR was 55.0% (95% CI, 31.5%-76.9%); the median DOR was not reached. The median PFS was 2.5 months (95% CI, 1.38-5.03), and the median OS was 12.6 months (95% CI, 5.78-NC). The 3-month OS rate was 91.3% (95% CI, 69.5%-97.8%), and the 6-month OS rate was 69.6% (95% CI, 46.6%-84.2%).

In patients with platinum-sensitive disease (n = 29), defined as a chemotherapy-free interval of 90 days or more, the ORR was 26.9% (95% CI, 11.6%-47.8%) and the DCR was 73.1% (95% CI, 52.2%-88.4%); the median DOR was 4.2 months (95% CI, 4.14-NC). The median PFS was 4.2 months (95% CI, 2.69-5.52), and the median OS was 11.2 months (95% CI, 8.38-NC).

“Treatment options for ES-SCLC in [the] second-line setting are limited,” wrote first study author Yun Fan, MD, of Zhejiang Cancer Hospital in Hangzhou, China, and coauthors in the presentation. “This combination of HTMC0435 and [temozolomide] showed promising antitumor activity and manageable safety both in [patients with] platinum-sensitive and platinum-resistant SCLC.”

The trial enrolled a total of 59 eligible patients with ES-SCLC who had progression after first- or second-line therapy. The trial was broken into 2 parts: a multicenter dose-escalation stage to evaluate safety and pharmacokinetics and a multicenter dose-expansion stage to evaluate preliminary efficacy.

In both stages, patients had histologically or cytologically confirmed recurrent or progressive ES-SCLC that was previously treated with 1 or 2 lines of therapy. Treatment also continued until disease progression or intolerable toxicity.

In the dose-escalation phase, a total of 4 patients received 16 mg of HTMC0435 in 8-mg doses twice daily and 75 mg/m2 of temozolomide once daily on days 1 to 7 of each 21-day cycle and a total of 3 patients received 12 mg of HTMC0435 in 6-mg doses twice daily and 75 mg/m2 of temozolomide once daily on days 1 to 7 of each 21-day cycle.

In the dose-expansion phase, a total of 52 patients received 16 mg of HTMC0435 in 8-mg doses twice daily and 75 mg/m2 of temozolomide once daily on days 1 to 7 of each 21-day cycle.

The recommended phase 2 dose (RP2D) was chosen to be HTMC0435 at 8 mg twice daily. Of patients who received the RP2D, brain and liver metastases were observed in 41.8% and 23.6% of patients, respectively. Additionally, 61.8% of patients received prior platinum-based and anti–PD-(L)1 therapy in the first-line setting.

The trial’s objectives were to evaluate the safety, pharmacokinetics, and preliminary efficacy of the treatment regimen.

Regarding safety, treatment-related adverse events (TRAEs) of any grade occurred in 69.6% of patients and TRAEs of grade 3 or 4 occurred in 55.9%. The most common TRAEs of grades 3 and 4 were neutropenia (35.6%), leukopenia (28.8%), thrombocytopenia (13.6%), and anemia (8.5%). TRAEs led to dose reduction of HTMC0435 in 10.2% of patients and treatment discontinuation in none.

Reference

Fan Y, Li H, Huang Z, et al. Efficacy and safety of HTMC0435 combination with temozolomide in relapsed extensive-stage small-cell lung cancer (ES-SCLC): a phase Ib/II study. J Clin Oncol. 2025;43(suppl 16):8097. doi:10.1200/JCO.2025.43.16_suppl.8097

Recent Videos
Data from the phase 3 DeLLphi-304 trial at ASCO 2025 revealed a survival advantage with tarlatamab vs chemotherapy in second-line ES-SCLC.
The FDA approval of tarlatamab in SCLC has received much press attention, according to Daniel R. Carrizosa, MD, MS.
According to Jorge Nieva, MD, there are a multitude of things that can be explored to enhance the treatment landscape for lung cancer.
James Ninia, MD, discussed a phase 2/3 trial seeking to answer whether complete consolidation offers more benefit than incomplete consolidation in SCLC.
Overall survival benefit was significant with complete vs incomplete consolidation therapy, but lost significance when stratified by disease burden.
James Ninia, MD, discussed treatment options for patients with extensive-stage small cell lung cancer undergoing metastasis-directed radiotherapy.
Eric Singhi, MD, and the Oncology Brothers presenting slides
Eric Singhi, MD, and the Oncology Brothers presenting slides
Eric Singhi, MD, and the Oncology Brothers presenting slides
Eric Singhi, MD, and the Oncology Brothers presenting slides
Related Content