A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response

Conditions

• Advanced Unresectable or Metastatic Solid Malignancy

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Entrectinib — DRUG
  Entrectinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 600 milligrams (mg) per day once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.
• Inavolisib — DRUG
  Inavolisib will be self-administered by participants orally at home (except on clinic days) at the same time each day, on a starting dose of 9 mg/day QD until disease progression, intolerable toxicity, or consent withdrawal.
• Alectinib — DRUG
  Alectinib will be self-administered by participants orally at home (except on clinic days), at the same times each day, on a starting dose of 600 mg twice a day (BID) until disease progression, intolerable toxicity, or consent withdrawal.
• Ipatasertib — DRUG
  Ipatasertib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg QD until disease progression, intolerable toxicity, or consent withdrawal.
• Atezolizumab — DRUG
  Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg for participants on Day 1 of each 21-day cycle until unacceptable toxicity or progressive disease (or loss of clinical benefit).
• Trastuzumab Emtansine — DRUG
  Trastuzumab emtansine will be administered at 3.6 mg per kilogram (kg) of body weight by IV infusion every 21 days (unless dose reduction and/or dose delays are required) until disease progression or unacceptable toxicity.
• Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf — DRUG
  PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab once every 3 weeks.
• Tucatinib — DRUG
  Tucatinib 300 mg will be administered orally BID continuously starting from Cycle 1 Day 1 onwards.
• Investigator's Choice of Chemotherapy — DRUG
  Chemotherapy will consist of docetaxel, paclitaxel, or capecitabine, as determined by the investigator, and will be administered per the respective package insert and institutional guidelines.
• Paclitaxel — DRUG
  The dose of paclitaxel is 80 mg/m2 administered by IV infusion on Days 1, 8, and 15 of each 28-day cycle. The paclitaxel infusion will be delivered over at least 60 minutes for each dose per institutional guidelines and administered after the oral dose of ipatasertib.
• Tiragolumab — DRUG
  Following the administration of atezolizumab and an observation period, participants will receive 600 mg tiragolumab at a fixed dose administered by IV infusion on Day 1 of each 21-day cycle.
• Pralsetinib — DRUG
  Pralsetinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg/day (four 100-mg capsules per day) once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.

Study Details

This is a Phase II, multicenter, non-randomized, open-label, multi-arm study designed to evaluate the safety and efficacy of targeted therapies as single agents or in rational, specified combinations in participants with advanced unresectable or metastatic solid tumors determined to harbor specific biomarkers. Patients will be enrolled based on local testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory. The multi-arm structure of the MyTACTIC study allows patients with solid tumors to be treated with a drug or drug regimen tailored to their biomarker identified at screening.

Key Dates

Start date

Jan 13, 2021

Status verified

Dec 2024

Primary completion

Dec 4, 2023

Completion

Feb 27, 2024

Study Design

Enrollment

252 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A: Entrectinib
  Participants in this treatment arm must have a positive tumor biomarker result for ROS1 gene fusion.
• Experimental: Arm B: Inavolisib
  Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.
• Experimental: Arm C: Alectinib
  Participants in this treatment arm must have a positive tumor biomarker result for ALK rearrangement tumors.
• Experimental: Arm D: Ipatasertib
  Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.
• Experimental: Arm E: Atezolizumab + Investigator's Choice of Chemotherapy
  Participants in this treatment arm must have a positive tumor biomarker result for either tumor mutational burden (TMB) high or microsatellite instability (MSI) high/deficient mismatch repair (dMMR).
• Experimental: Arm F: Trastuzumab Emtansine + Atezolizumab
  Participants in this treatment arm must have a positive tumor biomarker result for human epidermal growth factor receptor 2 (HER2) mutations or amplification without known TMB high or MSI high/dMMR.
• Experimental: Arm G: PH FDC SC
  Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
• Experimental: Arm H: PH FDC SC + Investigator's Choice of Chemotherapy
  Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
• Experimental: Arm I: Trastuzumab Emtansine + Tucatinib
  Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
• Experimental: Arm J: Trastuzumab Emtansine + Atezolizumab
  Participants in this treatment arm must have positive tumor biomarker results for HER2 mutation or amplification and TMB high or MSI high/dMMR.
• Experimental: Arm K: Ipatasertib + Atezolizumab
  Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.
• Experimental: Arm L: Ipatasertib + Atezolizumab
  Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.
• Experimental: Arm M: Ipatasertib + Paclitaxel
  Participants in this treatment arm must have a positive tumor biomarker results for PI3KCA activating mutations and either AKT1/2/3 activating mutation or PTEN loss/loss of function.
• Experimental: Arm N: Atezolizumab + Tiragolumab
  Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR.
• Experimental: Arm O: Pralsetinib
  Participants in this treatment arm must have a positive tumor biomarker result for RET fusion.

Primary Outcome Measure

Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors [ Time Frame: Up to 32 months ]

Locations (38)

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