First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumor

Sponsor

Scorpion Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05768139

Collaborator

(none)

160

Enrollment

Location

Arms

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study STX-478-101 is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 in participants with advanced solid tumors with certain mutations.

Part 1 will evaluate STX-478 as monotherapy in participants with breast cancer and other solid tumor types; Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with breast cancer.

Each study part will include a 28-day screening period, followed by treatment with STX 478 monotherapy or combination therapy. Participants will remain in the study part to which they are initially enrolled throughout their participation in the study (i.e., they will not move into other study parts).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Gynecologic Cancer HNSCC Solid Tumors, Adult	Drug: STX-478 Drug: Fulvestrant	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumor

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1.1: Dose Escalation (Breast) Cohort A0: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.	Drug: STX-478 STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor.
Experimental: Part 1.2-DE: Dose expansion at MTD Cohort A1: Gynecologic cancers Cohort A2: HNSCC Cohort A3: Other solid tumors not included in Cohorts A0, A1, or A2 Mutations for Cohorts A1, A2, and A3: PI3Kα H1047X mutations or other kinase domain mutations Cohort A4: Solid tumors expressing PI3Kα helical domain mutations (E542/E545)	Drug: STX-478 STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor.
Experimental: Part 1.2-DS: RP2D Selection (Breast) Recommended Phase 2 dose (RP2D) Cohort A0: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.	Drug: STX-478 STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor.
Experimental: Part 1.3: RP2D Expansion (Breast) Cohort A0: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.	Drug: STX-478 STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor.
Experimental: Part 2.1: RP2D Selection Cohort B: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.	Drug: STX-478 STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. Drug: Fulvestrant Fulvestrant will be administered according to local labeling. Other Names: Faslodex
Experimental: Part 2.2: RP2D Expansion Cohort B: HR+/HER2- breast cancer expressing PI3Kα H1047X mutations or other kinase domain mutations.	Drug: STX-478 STX-478 is a second generation, mutant-selective, oral PI3Kα small molecule allosteric inhibitor. Drug: Fulvestrant Fulvestrant will be administered according to local labeling. Other Names: Faslodex

Outcome Measures

Primary Outcome Measures

Part 1.1 (Dose Escalation): Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) [First 28 days of treatment]
Part 1.1 (Dose Escalation): Proportion of participants who experience at least 1 DLT during the first 28 days of treatment. [First 28 days of treatment]
Part 1.1 (Dose Escalation): Cmax of STX-478 [12 months]
Part 1.1 (Dose Escalation): AUC(0-inf) of STX-478 [12 months]
Part 1.1 (Dose Escalation): AUC(0-t) of STX-478 [12 months]
Part 1.1 (Dose Escalation): AUC(0-τ) of STX-478 [12 months]
Part 1.1 (Dose Escalation): Change from baseline in ctDNA levels. [12 months]
Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c] [12 months]
Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose. [12 months]
Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide. [12 months]
Part 1.1 (Dose Escalation): Objective response rate (ORR). [12 months]
Part 1.1 (Dose Escalation): Incidence of TEAEs/SAEs ≥ grade 2. [12 months]
Part 1.1 (Dose Escalation): Frequency of TEAEs according to CTCAE v5.0 criteria. [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): Cmax of STX-478 [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-inf) of STX-478 [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-t) of STX-478 [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-τ) of STX-478 [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): Change from baseline in ctDNA levels. [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c] [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose. [12 months]
RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide [12 months]
Parts 1.2-DS and 2.1 (RP2D Selection): ORR [12 months]
Parts 1.2-DS and 2.1 (RP2D Selection): Frequency counts and percentages of AEs based on MedDRA and CTCAE v5.0 [12 months]
Parts 1.2-DS and 2.1 (RP2D Selection): Proportion of participants with DLTs. [12 months]
Parts 1.2-DS and 2.1 (RP2D Selection): Change in ECOG performance status. [12 months]
Parts 1.2-DE, 1.3, and 2.2 (Dose Expansion): ORR defined as the percentage of participants with partial response or complete response based on RECIST 1.1. [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
Has a new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen within 12 months prior to screening
Has a tumor that harbors a documented PI3Kα mutation (see the cohort-specific criterion for cohort-specific mutation types) obtained either from tumor or plasma samples, determined by PCR or NGS-based assay as an FDA-approved test in US, or obtained as part of normal clinical care in a CLIA certified or similarly certified laboratory.
Has at least 1 measurable tumor lesion per RECIST 1.1
Is ≥18 years of age at the time of signing the ICF
Has an ECOG performance status score of 0 or 1 at screening

Key Exclusion Criteria:

Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
Has symptomatic brain or spinal metastases
Has a tumor with mutations/deletions in PTEN and activating mutations in AKT or mTOR confirmed by a CLIA-certified laboratory
Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 (based on FPG and HbA1c thresholds defined in the inclusion criteria) requiring antihyperglycemic medication
Cohorts A0, A1, A2, A3, A4, and B: Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances.
Has had treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to the initiation of study treatment up to a maximum washout period of 28 days
Has toxicities from previous anticancer therapies that have not resolved to baseline levels or CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy
Has had radiotherapy within 14 days before the initiation of study treatment