- TPST-1120 demonstrated monotherapy clinical benefit in patients with late-line advanced, poor-prognosis cancers where responses would be unexpected
- RECIST responses observed with TPST-1120 combined with anti-PD1 therapy in patients who previously progressed on anti-PD1/PDL1 therapy
- Potential biomarker for patient responsiveness to TPST-1120 identified and will be further explored
- TPST-1120 demonstrated the ability to reprogram the tumor microenvironment (TME) in a tumor type that is refractory to anti-PD1 with low tumor mutation burden
- TPST-1120 is also in an ongoing randomized global Phase 1b/2 clinical study in combination with the standard-of-care regimen of atezolizumab and bevacizumab in first-line patients with hepatocellular carcinoma
- Cash runway into 2024
- The monotherapy arm consisted of one of the more challenging groups of tumors to treat in a Phase 1 trial, e.g., dominated by patients with late-line pancreatic and cholangiocarcinoma (CCA), where he considered stable disease a “win.”
- A number of patients in the monotherapy arm had meaningfully-prolonged stable disease, showing that TPST-1120 has activity as a monotherapy
- Two patients with IDH1 mutated CCA, a mutation found in ~15-30% of intrahepatic CCA, had stable disease extending out to five and ten months, respectively, vs. less than three months for historical standard-of-care values, indicating that an IDH1 mutation is a potential biomarker for patient sensitivity to TPST-1120
- In the combination arm, two patients with renal cell carcinoma (RCC) and one with metastatic CCA achieved partial response when treated with the higher doses of TPST-1120 in combination with pembrolizumab
- Both RCC patients had progressed on prior anti-PD1 therapy, providing strong evidence that TPST-1120 overcomes resistance to anti-PD1 therapy
- The patient with metastatic CCA had received multiple lines of prior systemic therapy and was PDL1-negative, mismatch repair proficient, and had a TMB of less than 10 mutations per megabase, supporting that TPST-1120 can reprogram the TME in immune-resistant type cancers
TPST-1120 Monotherapy Results
In the monotherapy portion of the trial, 19 evaluable patients with late-line treatment-refractory solid tumors, including pancreatic, cholangiocarcinoma, and colorectal cancers, were treated with oral twice-daily TPST-1120. The results showed that 53% (10/19) of patients experienced clinical benefit in the form of disease control, including tumor shrinkage in 21% of the patients. Two patients with late-line CCA, an aggressive tumor type and disease setting usually unresponsive to therapy, including IO therapies, achieved durable stable disease and one of the patients achieved durable tumor shrinkage.
TPST-1120 and Nivolumab Combination Therapy Results
In the combination therapy portion of the trial, 15 evaluable patients with heavily-pretreated renal cell carcinoma, hepatocellular carcinoma (HCC) and CCA were treated with oral twice-daily TPST-1120 and the anti-PD-1 therapy, nivolumab. All of the HCC and RCC patients had received an approved anti-PD-1 therapy in at least one prior line of therapy and discontinued that treatment due to disease progression. Promising objective responses (RECIST v1.1) were observed in two patients with late-line RCC who had previously progressed on anti-PD-1 therapy without an objective response (ORR 50%, n=2/4, in evaluable RCC patients). A third RECIST response was observed in a patient with late-line, heavily pre-treated CCA, a tumor type generally not responsive to anti-PD-1 alone.
Notably, all three responders were treated at the two highest doses of TPST-1120 (ORR 30%, 3/10).
Safety
TPST-1120 was well tolerated as both a monotherapy and in combination with nivolumab. The majority of the treatment-related adverse events were Grade 1 and 2, and included nausea, fatigue and diarrhea. No dose-limiting toxicities were reported during dose escalation.
Financial Update
Following the
About TPST-1120
TPST-1120 is a first-in-class1 oral selective PPAR⍺ antagonist with a dual mechanism designed to target both tumor cells directly and suppressive immune cells in the tumor microenvironment. Both types of targeted cells are dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy and in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In addition to the study presented at ASCO, in collaboration with
About Tempest Therapeutics
Tempest Therapeutics is a clinical-stage oncology company advancing small molecules that combine both tumor-targeted and immune-mediated mechanisms with the potential to treat a wide range of tumors. The company’s two novel clinical programs are TPST-1120 and TPST-1495, antagonists of PPARα and EP2/EP4, respectively. Both TPST-1120 and TPST-1495 are advancing through clinical trials designed to study both agents as monotherapies and in combination with other approved agents. Tempest is also developing an orally-available inhibitor of TREX-1, a DNA repair enzyme that controls activation of the cGAS/
Forward Looking Statements
This press release contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended concerning
Investor Contact:
swheeler@wheelhouselsa.com
Media Contact:
Aljanae Reynolds
areynolds@tempesttx.com
1 If approved by the FDA
Source: Tempest Therapeutics
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