On June 9, 2022 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing therapies that combine both targeted and immune-mediated mechanisms, reported that key takeaways from the TPST-1120 clinical program provided by Mark Yarchoan, M.D., associate professor of oncology at Johns Hopkins School of Medicine, at its June 5th investor event held in connection with the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Press release, Tempest Therapeutics, JUN 9, 2022, View Source [SID1234615808]). The company also revised its cash guidance. Dr. Yarchoan also presented the TPST-1120 Phase 1 results in an oral presentation at ASCO (Free ASCO Whitepaper) on Tuesday, June 7.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Dr. Yarchoan reviewed and discussed TPST-1120 results both as a single agent and in combination with nivolumab in a webcast presentation that is available on the Tempest website at View Source His conclusions include:
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 $15 million private investment in public equity financing completed in April 2022, Tempest’s cash and cash equivalents are currently expected to be sufficient to fund its current operating plans into the first quarter of 2024.
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 (Free ASCO Whitepaper), in collaboration with F. Hoffmann La Roche, TPST-1120 is also advancing through a randomized, first-line, global, Phase 1b/2 clinical study in combination with the standard-of-care regimen of atezolizumab and bevacizumab in patients with advanced or metastatic hepatocellular carcinoma.