PRE-I-SPY Phase I/Ib Oncology Platform Program

Registration Number
NCT05868226
Lead Sponsor
QuantumLeap Healthcare Collaborative
Brief Summary

I-SPY Phase I/Ib (I-SPY-P1) is an open-label, multisite platform study designed to evaluate single agents or combinations in a metastatic treatment setting that may be relevant for breast cancer patients with the overall goal of moving promising drug regimens into the I-SPY 2 SMART Design Trial (NCT01042379) and/or other oncology-based trials in a timely man...

Detailed Description

The PRE-I-SPY/I-SPY-P1 study is a platform trial with multiple ongoing drug regimen arms. In most cases, the treatment arm will have a dose-finding group (Part 1) and a dose-expansion group (Part 2). Eligibility criteria will vary according to the experimental regimen. Participant eligibility may vary according to the arm or the part within the study arm, in...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
54
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)Fam-Trastuzumab Deruxtecan-NxkiThe 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.
PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)ALX148The 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 (ZW25, zani) + Tucatinib (TUKYSA®)ZanidatamabZanidatamab 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 as well as potently activating ADCC, ADCP, and CDC. 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. It is 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 patients with HER2 positive breast cancer.
PRE2 Zanidatamab (ZW25, zani) + Tucatinib (TUKYSA®)TucatinibZanidatamab 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 as well as potently activating ADCC, ADCP, and CDC. 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. It is 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 patients with HER2 positive breast cancer.
Primary Outcome Measures
NameTimeMethod
Overall Response Rate (ORR)Start of treatment to 12 months

To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.

Maximum Tolerated Dose (MTD)Start of treatment to the date of last participant at end of DLT observation period at highest dose level (estimated 6 months)

The maximum dose level (mg/kg) which is not eliminated.

Recommended Phase 2 Dose (RP2D)Start of treatment to the date of last participant at highest dose level (estimated 6 months)

Using all available data, computation of RP2D (mg/kg), which may not be the MTD.

Incidence of Dose Limiting Toxicities (DLTs) at each dose levelDLT observation period: Start of treatment to 21 days (Cycle 1)

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).

Duration of Response (DOR)Start of treatment to 12 months

To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.

Incidence of Adverse Events related to the treatmentStart of treatment to 30 days post treatment (estimated 12 -18 months)

Evaluate the number of adverse events related to the treatment according to the current version of CTCAE during the trial.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) - descriptiveStart of treatment to 12 months

To provide descriptive assessment of Progression Free Survival (PFS) of the new agents/regimens with certain advanced solid tumors and breast cancer

Clinical Benefit Rate (CBR) at 6 monthsStart of treatment to 6 months

To obtain preliminary Clinical Benefit Rate (CBR) at 6 months of participants treated with the new agents/regimens.

Trial Locations

Locations (6)

The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center

🇺🇸

Birmingham, Alabama, United States

The University of Chicago Medicine Comprehensive Cancer Center

🇺🇸

Chicago, Illinois, United States

UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital

🇺🇸

New Lenox, Illinois, United States

UChicago Medicine Orland Park

🇺🇸

Orland Park, Illinois, United States

University of Minnesota Masonic Cancer Center

🇺🇸

Minneapolis, Minnesota, United States

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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