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A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer.

ABSTRACT: Squamous cell carcinoma of the anorectal canal (SCCA) is a rare HPV-related malignancy that is steadily increasing in incidence. A high unmet need exists for patients with persistent loco-regional and metastatic disease. Axalimogene filolisbac (ADXS11-001) is an investigational immunotherapy that stimulates tumor-specific responses against HPV-associated cancers, and has demonstrated benefit in metastatic cervical cancer. We conducted this single-arm, multicenter, phase 2 trial in patients with persistent/recurrent, loco-regional or metastatic SCCA. Patients received ADXS11-001, 1 × 109 colony-forming units intravenously every 3 weeks. A Simon 2-stage design was used to test primary co-endpoints of overall response rate (ORR) and 6-month progression-free survival (PFS) rate. Study would proceed to full enrollment if ORR ? 10% or 6-month PFS rate ? 20%. Thirty-six patients were treated; 29 patients were evaluable for response. One patient had a prolonged partial response (3.4% ORR). The 6-month PFS rate was 15.5%. Grade 3 adverse event were noted in 10 patients, with the majority being cytokine-release symptoms; one grade 4 adverse event was noted. No grade 5 adverse events occurred. ADXS11-001 was safe and well-tolerated in patients with SCCA. However, this study did not meet either primary endpoint. ADXS11-001 may be more beneficial when administered in combination with other cytotoxic or targeted agents.

SUBMITTER: Eng C

PROVIDER: S-EPMC7170499 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer.

Eng Cathy C Fakih Marwan M Amin Manik M Morris Van V Hochster Howard S HS Boland Patrick M PM Uronis Hope H

Oncotarget 20200414 15

Squamous cell carcinoma of the anorectal canal (SCCA) is a rare HPV-related malignancy that is steadily increasing in incidence. A high unmet need exists for patients with persistent loco-regional and metastatic disease. Axalimogene filolisbac (ADXS11-001) is an investigational immunotherapy that stimulates tumor-specific responses against HPV-associated cancers, and has demonstrated benefit in metastatic cervical cancer. We conducted this single-arm, multicenter, phase 2 trial in patients with ...[more]

PMID: 32341753

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Project description:BACKGROUND:Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~?1%) but are relatively common (10-50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. Little is known about the incidence and clinical implication of these mutations in early recurrence events, such as local recurrences or newly diagnosed metastatic disease. METHODS:We collected 130 archival tumor samples from 103 breast cancer patients treated with endocrine therapy prior to their local/metastatic recurrence. The cohort consisted of 41 patients having at least 1 sample from local/loco-regional recurrence and 62 patients with metastatic disease (of whom 41 newly diagnosed and 28 with advanced disease). The 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) were analyzed either by targeted sequencing or by droplet digital PCR. Progression-free survival (PFS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were statistically tested by Kaplan-Meier analysis. RESULTS:The prevalence of ESR1 mutations was 5/41 (12%) in newly diagnosed metastatic patients and 5/28 (18%) for advanced metastases, detected at allele frequency >?1%. All mutations in advanced metastases were detected in patients previously treated with both tamoxifen (TAM) and aromatase inhibitors (AI). However, in newly diagnosed metastatic patients, 4/5 mutations occurred in patients treated with TAM alone. PFS on AI treatment in metastatic patients was significantly shorter for ESR1 mutation carriers (p?=?0.017). In the local recurrence cohort, ESR1 mutations were identified in 15/41 (36%) patients but only 4/41 (10%) were detected at allele frequency >?1%. Again, most mutations (3/4) were detected under TAM monotherapy. Notably, 1 patient developed ESR1 mutation while on neoadjuvant endocrine therapy. DFS and DRFS were significantly shorter (p?=?0.04 and p?=?0.017, respectively) in patients that had ESR1 mutations (>?1%) in their loco-regional recurrence tumor. CONCLUSIONS:Clinically relevant ESR1 mutations are prevalent in newly diagnosed metastatic and local recurrence of endocrine-treated breast cancer. Since local recurrences are amenable to curative therapy, these mutations may inform the selection of subsequent endocrine therapies.

Dataset Information

A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer.

Publications

A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer.

Similar Datasets

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