Anlotinib

The ALTER-G-001 phase II study enrolled adult patients with GI cancer and unresectable liver metastasis, divided into Cohort A (stage IV CRC) and Cohort C (other GI cancers). Patients received anlotinib plus CAPEOX (Cohort A) or SOC chemotherapy (Cohort C), with resectability assessed after six cycles. Eligible patients underwent surgery, while others received maintenance therapy until progression or toxicity. The primary endpoint was ORR, with secondary endpoints including PFS, OS, DCR, DoR, and conversion rate of liver metastasis. Statistical analysis was based on historical ORR data and ITT principle.

NMPA accepted an sNDA for penpulimab plus anlotinib as first-line treatment for advanced HCC, based on APOLLO/ALTN-AK105-III-02 study data showing improved PFS (6.9 vs 2.8 months) and OS (16.5 vs 13.2 months) compared to sorafenib. The combination was tolerable with manageable safety profiles.

Innovent Biologics to present 10 clinical data on novel oncology molecules at ESMO Asia 2024, including updated Phase 1 results of IBI343 in pancreatic cancer.

NMPA accepted penpulimab's sNDA for first-line advanced HCC, marking its fifth indication. Supported by ALTN-AK105-III-02 trial, penpulimab + anlotinib reduced progression/death risk by 47% vs sorafenib, and death risk by 31%. No new safety signals noted. Penpulimab's combination therapy for metastatic nasopharyngeal carcinoma also accepted by NMPA and FDA.

Akeso's penpulimab, a PD-1 monoclonal antibody, in combination with anlotinib, has had its supplemental new drug application accepted by China's NMPA for first-line treatment of advanced hepatocellular carcinoma (HCC). This marks penpulimab's fifth indication, supported by the ALTN-AK105-III-02 study, which showed significant improvements in progression-free survival and overall survival in HCC patients compared to sorafenib.

50 patients from 5 centers received protocol-specified therapy; 38% discontinued early. Median PFS was 14.9 months, and 1-year OS rate was 74.8%. 72% achieved objective response, with 83.3% of responders maintaining response >6 months. 92% experienced any grade AEs, and 78% had grade ≥3 events. 48% had immune-related AEs, with 6% experiencing grade ≥3 irAEs.

45 patients received sintilimab plus anlotinib concurrent with platinum-based doublet chemotherapy; 34 had squamous cell carcinoma, 33 stage III disease. 26 achieved pathologic complete response (pCR), 30 major pathologic response (MPR). Objective response rate (ORR) was 71.1%, disease control rate (DCR) 97.8%. Median follow-up was 22.8 months, with 24-month event-free survival (EFS) rate of 81.5%. All-grade treatment-related adverse events (TRAEs) occurred in 100% of patients, with immune-related AEs (irAEs) in 15.6%. Neoadjuvant treatment significantly decreased Treg cell infiltration and increased vascular normalization and perivascular CD4+ T cell infiltration in pCR patients.

Anlotinib, a multi-target TKI, is primarily metabolized by CYP3A4/5 and CYP1A2. A PBPK model predicts minimal significant DDIs with CYP3A/1A2 inhibitors, but significant reduction in anlotinib exposure with CYP3A inducers like rifampicin, emphasizing the need to avoid strong inducers.

Benmelstobart plus anlotinib demonstrated promising efficacy and low toxicity in Chinese EGFR-positive advanced NSCLC patients who progressed after EGFR TKI therapy, suggesting a potential chemotherapy-free immunotherapy option. The combination showed a mPFS of 9 months and a mOS of 28.9 months, with a DCR of 87.3% and a mDoR of 19.8 months, outperforming previous studies. The therapy's favorable safety profile and oral administration convenience highlight its potential in the evolving treatment landscape for this patient population.