Our Clinical Trials

Empowering novel cancer treatment options

Our Clinical Trials

We are currently conducting clinical trials of our investigational products in multiple cancer indications and expect to initiate additional clinical trials in the future. Select from the list below to learn more about our current and upcoming clinical trials and the cancers we seek to treat.

Hematologic Malignancies

Disease Background:

MDS is a collection of bone marrow disorders in which malignant hematopoietic cells prevent production of healthy, mature blood cells. Low blood cell counts, called cytopenias, are a hallmark feature of MDS and are a principal cause of morbidity and mortality from infection and bleeding. MDS can develop de novo or may arise secondary to chemotherapy or radiation treatment for a different, prior malignancy or following an antecedent hematological disorder. Treatment-related MDS is associated with increased complex chromosomal abnormalities and carries a worse prognosis than de novo MDS. MDS predominantly affects older adults, with approximately 75% of patients aged 60 years or older at diagnosis. Around 30% of patients diagnosed with MDS will progress to AML, with the rate being higher for patients with more advanced disease.

MDS patients are segmented into different risk groups according to the number of cytopenias, bone marrow blast percentage, and cytogenetic abnormalities. The presence of three or more coincident structural genetic abnormalities is classified as a complex karyotype, which correlates with poor prognosis, low response to intensive chemotherapy, high rate of relapse and inferior survival. Mutations in TP53 occur in approximately 20% of patients with de novo MDS and in more than 30% of patients with therapy-related MDS who develop disease secondary to chemotherapy or radiation treatment for other cancers. Sequencing of a panel of commonly mutated genes, including TP53, is standard practice in the diagnosis of MDS.

Historically, treatment response rates in TP53 mutant MDS patients have been poor regardless of therapy. There are no established curative pharmacologic therapies for MDS.


Additional Resources:

https://www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq


Our Progress:

We are conducting a randomized, controlled Phase 3 clinical trial to compare the rate of CR and duration of CR in patients with TP53 mutant MDS who receive APR-246 and azacitidine or azacitidine alone.

We are also conducting two Phase 1b/2 investigator-initiated trials to evaluate the potential benefit of APR-246 + azacitidine combination in the frontline treatment of TP53 mutant myeloid malignancies, including MDS. Data updates from these Phase 1b/2 trials were presented as oral abstracts at the American Society of Hematology Annual Meeting in December 2019.


Clinical Trial(s):

Disease Background:

AML is the most common form of adult leukemia, with the highest incidence in patients aged 60 years and older. AML is characterized by proliferation of abnormal immature white blood cells which, like MDS, impairs production of normal blood cells. AML can develop de novo or may arise secondary to progression of other hematologic disorders or from chemotherapy or radiation treatment for a different, prior malignancy; secondary AML carries a worse prognosis than de novo AML.

AML patients are segmented into different risk groups according to cytogenetic abnormalities. The presence of three or more coincident structural genetic abnormalities is classified as a complex karyotype, which correlates with adverse prognosis, low response to intensive chemotherapy, high rate of relapse and inferior survival. Mutations in TP53 occur in approximately 20% of patients with newly diagnosed AML, more than 30% of patients with therapy-related AML and approximately 70-80% of patients with complex karyotype. Sequencing of a panel of commonly mutated genes, including TP53, is standard practice in the diagnosis of AML.

Historically, treatment response rates in TP53 mutant AML patients have been poor regardless of therapy.


Additional Resources:

https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq


Our Progress:

We are conducting two Phase 1b/2 investigator-initiated trials to evaluate the potential benefit of APR-246 + azacitidine combination in the frontline treatment of TP53 mutant myeloid malignancies, including MDS. Data updates from these Phase 1b/2 trials were presented as oral abstracts at the American Society of Hematology Annual Meeting in December 2019.

We are also conducting a Phase 1 dose-finding and cohort expansion study to determine the safety and preliminary potential efficacy of APR-246 in combination with venetoclax and with or without azacitidine in the treatment of frontline and relapsed/refractory AML.


Clinical Trial(s):

Disease Background:

There are no established curative pharmacologic therapies for MDS or AML. Allogeneic hematopoietic stem cell transplant (allo‑HCT) is currently the only recognized therapy believed to increase the likelihood of long term survival for TP53 mutant MDS and AML patients. Unfortunately, many patients are not candidates for allo‑HCT due to lack of sufficient clinical response to initial therapy, advanced age, comorbidities or lack of a suitable donor. It is estimated that fewer than 10% of patients diagnosed with TP53 mutant MDS and AML undergo allo-HCT.

For those TP53 mutant MDS and AML patients who receive allo‑HCT, the post‑transplantation prognosis is poor: TP53 mutations are associated with a 4‑fold increased risk of death and 1‑year relapse‑free survival (RFS) of only 30% following transplantation.


Additional Resources:

https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq


Our Progress:

We are conducting a Phase 2 clinical trial to assess the safety and potential efficacy of APR-246 in combination with azaciditine as maintenance therapy after allo-HCT for patients with TP53 mutant MDS or AML.


Clinical Trial(s):

Disease Background:

Chronic lymphocytic leukemia (CLL) is one of the most common types of B-cell non-Hodgkin lymphoma (NHL), characterized by a progressive accumulation of functionally incompetent monoclonal lymphocytes.

CLL is associated with a highly heterogeneous disease course that is partly explained by the diverse genetic aberrations identified in CLL patients. In particular, deletions in chromosome 17p [del(17p)] and TP53 mutations belong to the strongest prognostic and predictive markers guiding treatment decisions in CLL. Del(17p) results in loss of one copy of the TP53 gene and is often accompanied by mutation in the remaining TP53 gene copy. TP53 mutation occurs in approximately 25% of all CLL and up to approximately 85% of del(17p) CLL.

TP53 mutant / del(17p) CLL is associated with impaired response to therapy and many patients will experience disease relapse and progression.


Additional Resources:

https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq


Our Progress:

We have designed and plan to conduct a Phase 1 clinical trial evaluating the adverse event profile and potential preliminary efficacy of APR‑246 with venetoclax and rituximab, and APR-246 with ibrutinib in R/R TP53 mutant CLL and MCL.


Clinical Trial(s):

  • expected start 2H 2020

Disease Background:

Mantle cell lymphoma (MCL) is an aggressive form of NHL that accounts for approximately 6% of all NHL cases. It is characterized by accumulation of malignant B lymphocytes in the outer edge, or mantle zone, of lymph node follicles.

There are two major variants of MCL, known as classical and leukemic non-nodal (L-NN). Classical nodal MCL, accounting for 80-90% of cases, affects the lymph nodes and extra nodal sites. In contrast, L-NN MCL involves the bone marrow, peripheral blood and spleen. Of these, classical MCL is the more aggressive disease. TP53 mutation / del(17p) are the most frequent findings in MCL. TP53 mutations occur in approximately 20% of cases and are associated with poor prognosis and resistance to first-line and later-line regimens.

There is no standard of care therapy for R/R MCL but ibrutinib is a preferred treatment option.


Additional Resources:

https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq


Our Progress:

We have designed and plan to conduct a Phase 1 clinical trial evaluating the adverse event profile and potential preliminary efficacy of APR‑246 with venetoclax and rituximab, and APR-246 with ibrutinib in R/R TP53 mutant CLL and MCL.


Clinical Trial(s):

  • expected start 2H 2020

Solid Tumors

Disease Background:

Gastric cancer includes cancers of the stomach and gastroesophageal junction. It is the fifth most common cancer worldwide and the third leading cause of cancer-related death. Gastric cancer is typically detected at an advanced stage and disease progression after first-line chemotherapy is common. TP53 mutation occurs in approximately 35-55% of gastric cancers, and up to 90% in high-risk populations.


Additional Resources:

https://www.cancer.gov/types/stomach/patient/stomach-treatment-pdq


Our Progress:

In preclinical studies, as reported by Ghosh and colleagues from Memorial Sloan Kettering Cancer Center at the 2019 AACR annual meeting, we have observed synergy in mouse cancer models when APR-246 was combined with immuno-oncology agents, including anti-PD-1.

We have designed and plan to conduct a Phase 1/2 clinical trial evaluating the adverse event profile and potential preliminary efficacy of APR-246 with anti-PD-1 therapy in R/R gastric cancer, bladder cancer and non-small cell lung cancer.


Clinical Trial(s):

  • expected start 2H 2020

Disease Background:

Bladder cancer is a common cancer worldwide, though it is more common in men than women. TP53 mutation occurs in approximately 50% of bladder cancer cases.


Additional Resources:

https://www.cancer.gov/types/bladder/patient/bladder-treatment-pdq


Our Progress:

In preclinical studies, as reported by Ghosh and colleagues from Memorial Sloan Kettering Cancer Center at the 2019 AACR annual meeting, we have observed synergy in mouse cancer models when APR-246 was combined with immuno-oncology agents, including anti-PD-1.

We have designed and plan to conduct a Phase 1/2 clinical trial evaluating the adverse event profile and potential preliminary efficacy of APR-246 with anti-PD-1 therapy in R/R gastric cancer, bladder cancer and non-small cell lung cancer.


Clinical Trial(s):

  • expected start 2H 2020

Disease Background:

Lung cancer is the most common cancer worldwide and the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 84% of all lung cancer diagnoses. TP53 mutation occurs in up to 80% of NSCLC cases.


Additional Resources:

https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq


Our Progress:

In preclinical studies, as reported by Ghosh and colleagues from Memorial Sloan Kettering Cancer Center at the 2019 AACR annual meeting, we have observed synergy in mouse cancer models when APR-246 was combined with immuno-oncology agents, including anti-PD-1.

We have designed and plan to conduct a Phase 1/2 clinical trial evaluating the adverse event profile and potential preliminary efficacy of APR-246 with anti-PD-1 therapy in R/R gastric cancer, bladder cancer and non-small cell lung cancer.


Clinical Trial(s):

  • expected start 2H 2020