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).
Click on the image below to watch the Live Virtual Grand Rounds (May 2023)
Summary of Cohort Activity in the TAPUR Study
The tables below display cohorts that have been closed or expanded to Stage II as of March 16, 2023.
Closed Cohorts
| Treatment | Cancer | Variant | Findings | Publications/Presentations |
|---|---|---|---|---|
| Abemaciclib | Esophagus | CDKN2A loss or mutation | Pending | Pending |
| Cetuximab | Breast | KRAS, NRAS, BRAF wild type | Negative |
Published Manuscript - Targeted Oncology - October 22, 2020 |
| 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 | Negative | Poster Presentation - 2023 AACR Annual Meeting - April 18, 2023 |
| 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 | Breast | Germline or somatic BRCA1/BRCA2 inactivating mutations | Pending | Pending |
| Colorectal | ATM mutation or deletion | Negative | Poster Presentation - 2023 ASCO GI Cancers Symposium - January 19, 2023 | |
| 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 Published Manuscript - JCO Precision Oncology - February 8, 2023 |
|
| Pancreatic | BRCA1/BRCA2 mutation | Positive | Poster Presentation - 2020 ASCO Virtual Meeting - May 29, 2020 | |
| Various Cancers (Collapsed) | Germline or somatic BRCA1/BRCA2 inactivating mutations | Positive | Poster Presentation - 2022 European Society for Medical Oncology - September 10, 2022 | |
| 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 Presentation - 2019 ASCO Annual Meeting - June 2, 2019 |
|
| Soft tissue sarcoma | CDK4 amplification | Positive | Poster Presentation - 2021 ASCO Annual Meeting - June 4, 2021 | |
| Various Cancers (Collapsed) | CDKN2A loss or mutation | Pending | Pending | |
| Various Cancers (Collapsed) | CDK4 amplification | Pending | Pending | |
| Various Cancers (Collapsed) | CDK6 amplification | Pending | Pending | |
| Pertuzumab + Trastuzumab | Colorectal | ERBB2/ERBB3 mutation | Negative | Published Manuscript - JCO Precision Oncology - October 31, 2022 |
| Colorectal | ERBB2 amplification or overexpression | Positive |
Poster Presentation - 2020 ASCO GI Cancers Symposium in San Francisco, CA - January 25, 2020 Published Manuscript - JCO Precision Oncology - October 31, 2022 |
|
| Bronchus and lung | ERBB2/ERBB3 amplification, mutation, or overexpression | Positive | Poster Presentation - 2022 European Society for Medical Oncology - September 12, 2022 | |
| Uterine | ERBB2/ERBB3 amplification, mutation, or overexpression | Positive |
Oral Presentation - 2021 ASCO Annual Meeting - June 7, 2021 Published Manuscript - JCO Precision Oncology - April 7, 2023 |
|
| Gallbladder and bile ducts | ERBB2/ERBB3 amplification, mutation, or overexpression | Positive | Poster Presentation - 2023 ASCO GI Cancers Symposium in San Francisco, CA - January 19, 2023 | |
| Pembrolizumab | Metastatic breast | High tumor mutational burden | Positive | Poster Presentation - 2019 ASCO Annual Meeting - June 2, 2019 Published Manuscript - Journal of Clinical Oncology - April 12, 2021 |
| Colorectal |
High tumor mutational burden |
Positive | Poster Presentation - 2020 ASCO GI Cancers Symposium in San Francisco, CA - January 25, 2020 | |
| Various Cancers (Collapsed) | High tumor mutational burden | Pending | Pending | |
| Regorafenib | Various Cancers (Collapsed) | BRAF mutation or amplification | Pending | Pending |
| Sunitinib | Breast | FGFR1 mutation or amplification | Positive | Poster Presentation - 2021 AACR Annual Meeting - April 10, 2021 |
| Breast | FGFR2 mutation or amplification | Pending | Pending | |
| Colorectal | FLT-3 mutation or amplification | Negative |
Published Manuscript - Targeted Oncology - October 17, 2020 |
|
| Talazoparib | Colorectal | Germline or somatic BRCA1/BRCA2 mutation | Pending | Pending |
| Various Cancers (Collapsed) | Pending | Pending | ||
| Temsirolimus | Colorectal | PIK3CA mutation | Negative | Poster Presentation - 2022 ASCO GI Cancers Symposium - January 20, 2022 |
| Breast | PIK3CA mutation | Pending | Pending | |
| Various Cancers (Collapsed) | AKT1 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 | Positive | Poster Presentation - 2023 AACR Annual Meeting - April 18, 2023 | |
| Vemurafenib + Cobimetinib | Colorectal | BRAF_V600E/D/K/R mutation | Positive |
Poster Presentation - 2020 ASCO GI Cancers Symposium in San Francisco, CA - January 25, 2020 Published Manuscript - JCO Precision Oncology - November 21, 2022 |
| 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 |
| Head and Neck Cancer | CDKN2A loss or mutation | |
| Soft tissue sarcoma | 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 | 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 | |
| Talazoparib | Various Cancers (Collapsed) | ATM mutation |
| Various Cancers (Collapsed) | PALB2 mutation | |
| Temsirolimus | Uterine | PIK3CA mutation |
| Vemurafenib + Cobimetinib | Gallbladder and Bile Ducts | BRAF_V600E/D/K/R mutation |
| Tucatinib + Trastuzumab SC | Bronchus and lung | ERBB2 mutation, amplification, or overexpression |