PRE-ISPY Phase I/II Oncology Platform Program

Conditions

• Adenocarcinoma
• Adenocarcinoma of Colon
• Colo-rectal Cancer
• Colon Cancer
• Colonic Neoplasms
• Colorectal Neoplasms
• ER Positive Breast Cancer
• Estrogen Receptor Positive Tumor
• HER-2 Protein Overexpression
• HER2 Low Breast Cancer
• HER2 Low Breast Carcinoma
• HER2 Mutation-Related Tumors
• HER2-negative Breast Cancer
• HER2-positive Breast Cancer
• HER2-positive Metastatic Breast Cancer
• HR Positive
• Hormone Receptor Negative Breast Carcinoma
• Hormone Receptor-positive Breast Cancer
• Metastatic
• Metastatic Breast Cancer
• Metastatic Cancer
• Minimal Residual Disease
• Neoplasm, Residual
• PR-positive Breast Cancer
• Progesterone Receptor-positive Breast Cancer
• Rectal Cancer
• Rectal Neoplasms
• Solid Carcinoma
• Solid Tumor
• Solid Tumor, Adult
• Triple Negative Breast Cancer
• ctDNA Monitoring

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 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

Study Details

PRE-ISPY Phase I/II (I-SPY-P1) is an open-label, multisite platform study with multiple ongoing drug regimen arms added by protocol amendment which is designed to evaluate single agents or combinations in locally advanced, incurable, or metastatic solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence following prior treatment with curative intent. The overall goal is moving promising drug regimens into a larger phase II (or III) trial and in general could feed the neoadjuvant breast I-SPY 2 Trial (NCT01042379) and/or other oncology solid tumor trial in a timely manner.

Key Dates

First listed

May 22, 2023

Start date

Feb 15, 2023

Status verified

Aug 2026

Primary completion

Dec 30, 2030

Completion

Dec 30, 2031

Study Design

Enrollment

280 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)
  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.
• Experimental: PRE2 Zanidatamab (Ziihera®, ZW25, zani) + Tucatinib (TUKYSA®)
  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.
• Experimental: PRE4 TTX-MC138
  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.

Primary Outcome Measure

Incidence of Adverse Events related to the treatment [ Time Frame: Start of treatment to 30 days post treatment (estimated 12 -18 months) ]

Central Contacts

• Smita M Asare
  (855) 866-0505
  [email protected]
• Maria Pitsiouni, PhD
  (415) 651-8047
  [email protected]

Locations (10)

Find similar trials in Birmingham, AL

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