Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ALX148 · 1 trial · 32 indications
Evaluate the number of adverse events related to the treatment according to the current version of CTCAE during the trial.
To determine the safety and tolerability of new agents/regimens in participants with certain advanced solid tumors and breast cancer. DLT rate (number of participants who experience a protocol defined DLT/total number of DLT cohort participants at that dose).
The maximum dose level (mg/kg) which is not eliminated.
Using all available data, computation of RP2D (mg/kg), which may not be the MTD.
To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.
To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.
| Arm | Type | Description |
|---|---|---|
| PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®) | EXPERIMENTAL | The combination of T-DXd and ALX148 aims to explore the anti-tumoral effects of trastuzumab, of the topoisomerase inhibitor DXd and of the CD47-blocking agent ALX148. The rationale for this combination is that ALX148 is hypothesized, based on preclinical data, to facilitate antibody-dependent cellular phagocytosis (ADCP) of HER2 expressing (\>HER2 1+) breast cancer binding T-DXd while cancer cell intrinsic or bystander cytotoxicity of T-DXd will result in the release of neoantigens promoting immune mediated antitumor activity in the tumor microenvironment. |
| PRE2 Zanidatamab (Ziihera®, ZW25, zani) + Tucatinib (TUKYSA®) | EXPERIMENTAL | Zanidatamab is a bispecific IgG1-like antibody directed against two distinct HER2 epitopes. It induces formation of receptor clusters and internalization resulting in downregulation. It also inhibits growth factor-dependent and -independent tumor cell proliferation and potently activates ADCC, ADCP, and CDC. FDA approved for metastatic HER2+ bile duct cancer. Tucatinib is a highly selective, small molecule tyrosine kinase inhibitor (TKI) of HER2 compared to other TKI's (i.e., EGFR). It is well tolerated, crosses the blood brain barrier and can treat CNS disease. FDA approved for HER2+ breast cancer. Given the promising clinical data for each of these drugs which have different mechanisms, the effect of zanidatamab after T-DXd (Enhertu®) in breast cancer patients, and the favorable toxicity profile of both drugs, we hypothesize that the combination of tucatinib and zanidatamab will be well tolerated and more efficacious than either drug alone for the treatment of HER2+ breast cancer. |
| PRE4 TTX-MC138 | EXPERIMENTAL | TTX-MC138 is an antisense oligonucleotide targeting miR-10b. MicroRNA-10b (miR-10b) was identified in metastatic cell lines and tumors from participants with metastatic breast cancer and has been shown to regulate the ability of metastatic tumor cells to survive outside of the primary tumor and to migrate and invade surrounding tissue. miRNA-10b is critical to tumor growth and is a master regulator of metastatic cell viability in a range of cancers, including breast, pancreatic, ovarian, colon cancer, glioblast. This is a PRE-ISPY PHASE II study of TTX-MC138 as interception treatment in patients with Stage I-III adenocarcinoma of the colon or rectum (Cohort A) who have documented minimal residual disease by tumor informed ctDNA, that was collected following completion of standard therapy with curative intent. |
| Name | Type | Description |
|---|---|---|
| ALX148 | DRUG | Starting dose Dose Level 1 30mg/kg IV Q3W; Dose Level Minus 1 20 mg/kg IV Q3W (if needed); Dose Level 2 45 mg/kg IV Q3W; |
| Fam-Trastuzumab Deruxtecan-Nxki | DRUG | 5.4 mg/kg IV Q3W; allowed to dose reduce after DLT observation period |
| Zanidatamab | DRUG | 20 mg/kg IV Q2W on Day 1 and Day 15 of each 28 day cycle |
| Tucatinib | DRUG | Dose Level 1: 300 mg PO BID daily; Dose Leve Minus 1: 250 mg PO BID daily |
| TTX-MC138 | DRUG | 4.8 mg/kg Q4W IV on Day 1 for up to 12 cycles as interception therapy |
General Inclusion Criteria (GIC): * GIC1: The participant must have ability to understand and willingness to provide signed written informed consent prior to any study related assessments and procedures and for collection of archival FFPE blocks for research. If FFPE blocks cannot be submitted, 20 ...