Therapy with the potent, selective, potential first-in-class MAT2A inhibitor IDE397 induced responses in sufferers with regionally superior or metastatic urothelial most cancers or non–small cell lung most cancers (NSCLC) harboring MTAP deletions, in accordance with outcomes from a part 2 dose-expansion trial (NCT04794699).1
Findings confirmed that efficacy-evaluable sufferers (n = 18) achieved an general response fee of 38.9%, which included 1 full response (CR) and 6 partial responses (PRs). The CR and a pair of PRs have been noticed in sufferers with urothelial most cancers, and three PRs have been reported in sufferers with NSCLC. Moreover, 2 PRs have been awaiting affirmation in 1 affected person with urothelial most cancers who skilled a 100% tumor discount within the goal lesion and in 1 affected person with NSCLC adenocarcinoma.
Moreover, 10 sufferers achieved steady illness, and the illness management fee was 94%. Tumor shrinkage was reported in 78% of sufferers.
“We’re extremely inspired by the preliminary medical efficacy and favorable security profile noticed with IDE397 on the 30-mg, once-a-day growth dose, together with a number of PRs responses and 1 CR by RECIST 1.1 [criteria] in [patients with] MTAP-deletion urothelial and lung most cancers,” Darrin Beaupre, MD, PhD, chief medical officer of IDEAYA Biosciences, acknowledged in a information launch. “As well as, at this growth dose we noticed a good opposed [effect (AE)] profile with no drug-related critical AEs and mid-single digit % grade 3 or increased drug-related AEs, which we consider has the potential to allow longer length dosing in addition to combos.”
The part 2 dose-expansion examine stemmed from a part 1 dose-escalation examine evaluating IDE397 in grownup sufferers with regionally superior or metastatic strong tumors harboring MTAP deletions. The continuing examine is enrolling sufferers a minimum of 18 years of age who skilled illness development after a minimum of 1 prior line of remedy or have been illiberal to extra customary remedy. Homozygous lack of MTAP or MTAP deletion is required.2
Different key inclusion standards encompass measurable illness; an ECOG efficiency standing of 0 or 1; sufficient organ perform; and restoration from acute results of prior remedy.
Key exclusion standards embrace recognized symptomatic mind metastases; recognized main central nervous system malignancies; present energetic liver or biliary illness; impaired gastrointestinal perform; energetic, uncontrolled an infection; clinically vital cardiac abnormalities; prior remedy with a MAT2A inhibitor, PRMT inhibitor, and/or sacituzumab govitecan-hziy (Trodelvy); systemic anti-cancer remedy or main surgical procedure inside 4 weeks of enrollment; radiation remedy inside 2 weeks of enrollment; and prior irradiation to greater than 25% of the bone marrow.
The examine is evaluating escalating doses of IDE397 alone, together with docetaxel and paclitaxel, and together with sacituzumab govitecan.2 Within the monotherapy dose-expansion cohort, sufferers with urothelial most cancers or NSCLC are receiving the agent at 30 mg as soon as per day.1
The first finish factors of the examine are the incidence of dose-limiting toxicities; establishing the utmost tolerated dose and/or really helpful part 2 dose; and preliminary antitumor exercise.2
In sufferers with urothelial most cancers or NSCLC enrolled within the part 2 dose-expansion cohort, the median variety of prior strains of remedy was 2 (vary, 1-7). The efficacy-evaluable inhabitants included 7 sufferers with urothelial most cancers, 4 sufferers with adenocarcinoma NSCLC, and seven sufferers with squamous NSCLC.1
Extra findings confirmed that on the information cutoff, 11 of 18 sufferers remained on remedy. Among the many 7 responders, 5 have been nonetheless responding to remedy per RECIST 1.1 standards. The median length of remedy, length of response, and progression-free survival weren’t but reached.
Moreover, the circulating tumor DNA (ctDNA) molecular response fee was 81%, with 13 of 16 evaluable sufferers experiencing a discount in ctDNA of a minimum of 50%.
Concerning security, drug-related grade 3 or increased AEs occurred in 5.6% of sufferers handled within the 30-mg growth cohort, and no sufferers skilled critical drug-related AEs.
Enrollment has began within the part 1 portion of the trial investigating IDE937 together with sacituzumab govitecan. Moreover, an ongoing part 1/2 trial (NCT05975073) can be evaluating IDE397 together with AMG 193 for sufferers with NSCLC harboring MTAP deletions.
References
- IDEAYA publicizes optimistic interim part 2 monotherapy growth information for IDE397 a possible first-in-class MAT2A inhibitor in MTAP-deletion urothelial and lung most cancers. Information launch. IDEAYA Biosciences. July 8, 2024. Accessed July 15, 2024. https://ir.ideayabio.com/2024-07-08-IDEAYA-Proclaims-Optimistic-Interim-Section-2-Monotherapy-Growth-Information-for-IDE397-a-Potential-First-in-Class-MAT2A-Inhibitor-in-MTAP-Deletion-Urothelial-and-Lung-Most cancers
- Research of IDE397 in individuals with strong tumors harboring MTAP deletion. ClinicalTrials.gov. Up to date June 27, 2024. Accessed July 15, 2024. https://clinicaltrials.gov/examine/NCT04794699
