garsorasib (D-1553)

P1/2, N=22, Terminated, InventisBio Co., Ltd | Phase classification: P1b/2 --> P1/2 | N=144 --> 22 | Trial completion date: Dec 2024 --> Jun 2024 | Recruiting --> Terminated; Adjustment of drug development strategy.

P1/2, N=225, Completed, InventisBio Co., Ltd | Active, not recruiting --> Completed

P1/2, N=92, Recruiting, InventisBio Co., Ltd | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=45, Completed, InventisBio Co., Ltd | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Feb 2024

The results show that garsorasib has a high response rate, long duration of response, and an acceptable and manageable safety profile in patients with previously treated KRASG12C-mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population.

P1/2, N=126, Not yet recruiting, Suzhou Genhouse Bio Co., Ltd.

P3, N=522, Recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Not yet recruiting --> Recruiting

P3, N=522, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P1/2, N=200, Active, not recruiting, InventisBio Co., Ltd | Trial primary completion date: Sep 2023 --> Apr 2024

P1/2, N=140, Recruiting, InxMed (Shanghai) Co., Ltd. | Enrolling by invitation --> Recruiting

P1/2, N=200, Active, not recruiting, InventisBio Co., Ltd | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2024 --> Sep 2023

P1/2, N=140, Enrolling by invitation, InxMed (Shanghai) Co., Ltd.

The most common grade ≥ 3 AEs were Alaninetransaminase (ALT) or Aspartatetransaminase (AST) increased and diarrhea. Sotorasib, Adagrasib, and Garsorasib as the drugs of choice for patients with KRAS mutation NSCLC, have definite efficacy and acceptable safety, especially for patients with advanced or metastatic disease and within posterior line therapy.

P1/2, N=92, Recruiting, InventisBio Co., Ltd | Not yet recruiting --> Recruiting

P1/2, N=203, Active, not recruiting, InventisBio Co., Ltd | Recruiting --> Active, not recruiting

Conclusions D-1553 is well tolerated and has shown promising anticancer activity in pts with pre-treated KRAS G12C mutated advanced PCa. This study is ongoing, and more results will be presented at the meeting.

Conclusions Combination of D-1553 and cetuximab showed an acceptable safety profile and achieved a higher response rate than D-1553 monotherapy and a promising PFS in heavily pretreated pts with KRAS G12C mutated CRC. More data will be presented at the meeting.

Compared to the KRAS WT and KRAS cell lines, D-1553 selectively inhibited cell viability in multiple KRAS cell lines, and the potency was slightly superior to sotorasib and adagrasib. The combination of D-1553 with chemotherapy, MEK inhibitor, or SHP2 inhibitor showed stronger potency on tumor growth inhibition or regression compared to D-1553 alone. These findings support the clinical evaluation of D-1553 as an efficacious drug candidate, both as a single agent or in combination, for patients with solid tumors harboring KRAS mutation.

Other Kras G12C inhibitors like D-1553, Sotorasib in combination with 2nd line chemotherapy are under investigation. Both Adagrasib and Sotorasib showed promising results in the pretreated Kras G12C pancreatic cancer patients with acceptable safety profile. Further exploration of these drugs and their combination with other chemotherapeutic agents is necessary. >

D-1553 demonstrated a tolerable safety profile and promising monotherapy activity in pts with heavily pretreated locally advanced or metastatic CRC and KRAS G12C mutations. This study is ongoing to further evaluate the safety and efficacy of D-1533 as monotherapy and in combination with cetuximab or chemotherapy in pts with locally advanced or metastatic CRC. Clinical trial information: NCT04585035.

P1/2, N=200, Recruiting, InventisBio Co., Ltd | Trial completion date: Feb 2023 --> Feb 2025 | Trial primary completion date: Nov 2022 --> Nov 2024

P1b/2, N=144, Recruiting, InventisBio Co., Ltd | Not yet recruiting --> Recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Apr 2023 --> Apr 2024

D-1553 represents a promising therapeutic option for patients with KRAS G12C-mutated NSCLC with a well-tolerated safety profile and encouraging anti-tumor activity.

P1/2, N=92, Not yet recruiting, InventisBio Co., Ltd | Initiation date: Jun 2022 --> Sep 2022

D-1553 was well tolerated, with promising antitumor activity in heavily pretreated KRAS G12C mutant-NSCLC patients. The study is ongoing, and more results will be presented at the meeting.

P1/2, N=203, Recruiting, InventisBio Co., Ltd

P1/2, N=92, Not yet recruiting, InventisBio Co., Ltd

D-1553 is well tolerated with no DLTs at studied doses. Early results demonstrate significant anti-tumor activity of single-agent D-1553 in pts with KRASG12C mutated NSCLC. This study is ongoing.

In patients with KRASG12C mutated solid tumor, D-1553 is well tolerated with no DLTs at studied doses. The RP2D has been determined to be 600 mg BID. Preliminary efficacy results demonstrate promising clinical activity of single-agent D-1553 in pts with KRASG12C mutated solid tumor.

These observations from PDX models support the combination treatment as a key to increased overall response rate to KRas G12C inhibitor in clinical trial. D-1553 is currently in a Phase 1/2 clinical trial for patients with advanced solid tumors harboring KRas G12C mutation (NCT04585035).

These data suggest that D-1553 has anti-tumor activity in a broad spectrum of cancers and is suitable for tissue-agnostic clinical development targeting cancers with KRas-G12C mutation. D-1553 is currently in a Phase 1/2 clinical trial evaluating safety, tolerability, PK and efficacy in patients with advanced solid tumors harboring KRasG12C mutation (NCT04585035).

P1/2, N=200, Recruiting, InventisBio Inc. | Not yet recruiting --> Recruiting

P1/2, N=200, Not yet recruiting, InventisBio Inc.