TAPUR Study Analysis Plan and Current Status

The TAPUR Study is a phase II, non-randomized, open-label clinical trial that aims to define signals of drug activity. Participants are enrolled in cohorts defined by tumor type, genomic alteration, and study drug. Initially, up to 10 participants are enrolled in a cohort and assessed for treatment response or lack of tumor growth for at least 16 weeks. If fewer than 2 participants have a successful outcome, the cohort is permanently closed to further enrollment. If two or more participants have successful outcomes, the cohort is expanded to enroll an additional 18 participants. Once complete data from a cohort become available, the TAPUR Study Data and Safety Monitoring Board (DSMB) will review the cohort results. A signal of drug activity will be declared if at least 7 of the 28 participants experience a treatment response or a lack of tumor growth for at least 16 weeks. ASCO will then publish these study findings in peer-reviewed journals to inform clinical practice and future research.

Rationale and Design of the TAPUR Study (published in JCO Precision Oncology, 2018).

Summary of Cohort Activity in the TAPUR Study

The tables below display cohorts that have been closed or expanded to Stage II as of May 13, 2022.

Closed Cohorts

Treatment Cancer Variant Findings Publications/Presentations
Cetuximab Breast KRAS, NRAS, BRAF wild type Negative

Published Manuscript - Targeted Oncology - October 22, 2020
Poster Presentation - 2019 AACR Annual Meeting - April 2, 2019

Non-small cell lung (NSCLC) KRAS, NRAS, BRAF wild type Negative
Ovarian KRAS, NRAS, BRAF wild type Negative
Crizotinib Various Cancers (Collapsed) MET amplification or mutation Pending Pending
Nivolumab + Ipilimumab Colorectal ATM mutation Pending Pending
Colorectal High tumor mutational burden Negative Poster Presentation - 2022 ASCO GI Cancers Symposium - January 20, 2022
Ovarian  BRCA1/BRCA2 mutation Pending Pending
Various Cancers (Collapsed) ATM mutation Pending Pending
Olaparib Colorectal ATM mutation or deletion Pending Pending
Various Cancers (Collapsed) ATM mutation or deletion Positive Poster Presentation - 2022 AACR Annual Meeting - April 11, 2022
Prostate BRCA1/BRCA2 mutation Positive Poster Presentation -  2020 ASCO Virtual Meeting - May 29, 2020
Pancreatic BRCA1/BRCA2 mutation Positive Poster Presentation -  2020 ASCO Virtual Meeting - May 29, 2020
Various Cancers (Collapsed) Germline or somatic BRCA1/BRCA2 inactivating mutations Pending Pending
Palbociclib Gallbladder and bile ducts CDKN2A loss or mutation Negative Published Manuscript - JCO Precision Oncology - August 14, 2019
Poster Presentation -  2018 ASCO Annual Meeting - June 4, 2018
Head and neck CDKN2A loss or mutation Positive Poster Presentation - 2021 ASCO Annual Meeting - June 4, 2021
Pancreatic CDKN2A loss or mutation Negative Published Manuscript - JCO Precision Oncology - August 14, 2019
Poster Presentation - 2018 ASCO Annual Meeting - June 4, 2018
Non-small cell lung (NSCLC) CDKN2A alterations Positive Published Manuscript - JCO Precision Oncology - June 25, 2020
Poster Presentation2019 ASCO Annual Meeting - June 2, 2019
Soft tissue sarcoma CDK4 amplification Positive Poster Presentation - 2021 ASCO Annual Meeting - June 4, 2021
Various Cancers (Collapsed) CDK4 amplification Pending Pending
Various Cancers (Collapsed) CDK6 amplification Pending Pending
Pertuzumab + Trastuzumab Colorectal ERBB2/ERBB3 mutation Pending Pending
Colorectal ERBB2 amplification or overexpression Positive Poster Presentation2020 ASCO GI Cancers Symposium in San Francisco, CA - January 25, 2020
Bronchus and lung ERBB2/ERBB3 amplification, mutation, or overexpression Pending Pending
Uterine ERBB2/ERBB3 amplification, mutation, or overexpression Positive

Oral Presentation - 2021 ASCO Annual Meeting - June 7, 2021

Gallbladder and bile ducts ERBB2/ERBB3 amplification, mutation, or overexpression Pending Pending
Pembrolizumab Metastatic breast High tumor mutational burden Positive Poster Presentation2019 ASCO Annual Meeting - June 2, 2019
Published Manuscript - Journal of Clinical Oncology - April 12, 2021
Colorectal

High tumor mutational burden

Positive Poster Presentation2020 ASCO GI Cancers Symposium in San Francisco, CA - January 25, 2020
Various Cancers (Collapsed) High tumor mutational burden Pending Pending
Sunitinib Breast FGFR1 mutation or amplification Positive Poster Presentation - 2021 AACR Annual Meeting - April 10, 2021
Colorectal FLT-3 mutation or amplification Negative

Published Manuscript - Targeted Oncology - October 17, 2020
Poster Presentation - 2019 AACR Annual Meeting - April 2, 2019

Temsirolimus Colorectal PIK3CA mutation Negative Poster Presentation - 2022 ASCO GI Cancers Symposium - January 20, 2022
Breast PIK3CA mutation Pending Pending
Various Cancers (Collapsed) mTOR mutation/amplification Positive Poster Presentation 2022 ASCO Annual Meeting - June 5, 2022
Various Cancers (Collapsed) PIK3CA mutation Pending Pending
Various Cancers (Collapsed) PTEN mutation Pending Pending
Vemurafenib + Cobimetinib Colorectal BRAF_V600E/D/K/R mutation Positive Poster Presentation - 2020 ASCO GI Cancers Symposium in San Francisco, CA - January 25, 2020
Various Cancers (Collapsed) BRAF_V600E/D/K/R mutation Positive Oral Presentation - 2022 ASCO Annual Meeting - June 7, 2022

Expanded Cohorts

Treatment Cancer Variant
Abemaciclib Bronchus and Lung CDKN2A loss or mutation
Atezolizumab + Talazoparib Various Cancers (Collapsed)  Germline or somatic BRCA1/BRCA2 mutation
Various Cancers (Collapsed) Non-BRCA DNA repair deficiency genes (Germline or somatic mutation: PALB2, ATM, ATR, CHEK2, FANCA, RAD51C, NBN, MLH1, MRE11A, CDK12)
Nivolumab + Ipilimumab Breast BRCA1/BRCA2 mutation
Breast High tumor mutational burden
Pancreatic BRCA1/BRCA2 mutation
Colorectal BRCA1/BRCA2 mutation
Prostate BRCA1/BRCA2 mutation
Pancreatic ATM mutation
Breast ATM mutation
Olaparib Breast Somatic or germline inactivating mutations in BRCA1 or BRCA2
Bronchus and lung Somatic or germline inactivating mutations in BRCA1 or BRCA2
Bronchus and lung ATM mutation or deletion
Gallbladder and bile ducts Somatic or germline inactivating mutations in BRCA1 or BRCA2
Pancreatic ATM mutation or deletion
Uterine Somatic or germline inactivating mutations in BRCA1 or BRCA2
Palbociclib Bronchus and lung CCND1 amplification
Soft tissue sarcoma CDKN2A loss or mutation
Ovarian CDKN2A loss or mutation
Bone and Cartilage  CDKN2A loss or mutation
Pembrolizumab Esophagus High tumor mutational burden
Gallbladder and bile ducts High tumor mutational burden
Ovarian High tumor mutational burden
Pancreatic High tumor mutational burden
Uterine High tumor mutational burden
Pertuzumab + Trastuzumab Bladder ERBB2/ERBB3 amplification, mutation, or overexpression
Breast ERBB2/ERBB3 mutation or ERBB3 amplification
Head and Neck ERBB2/ERBB3 amplification, mutation, or overexpression
Ovarian  ERBB2/ERBB3 amplification, mutation, or overexpression
Pancreatic ERBB2/ERBB3 amplification, mutation, or overexpression
Regorafenib Bronchus and lung BRAF mutation or amplification
Sunitinib Colorectal FGFR1 mutation or amplification
Gallbladder and bile ducts FGFR2 mutation or amplification
Temsirolimus Uterine  PIK3CA mutation
Vemurafenib + Cobimetinib Gallbladder and Bile Ducts BRAF_V600E/D/K/R mutation