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

• ClinicalTrials.gov Identifier: NCT05768139
• Recruitment Status: Recruiting
• Last Update Posted: March 14, 2023
• Sponsor: Scorpion Therapeutics, Inc.
• Information provided by (Responsible Party): Scorpion Therapeutics, Inc.

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
• Estimated 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
• Estimated Study Start Date: March 2023
• Estimated Primary Completion Date: June 1, 2026
• Estimated Study Completion Date: June 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 Name: 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 Name: Faslodex

Outcome Measures

Primary Outcome Measures :

1. Part 1.1 (Dose Escalation): Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) [ Time Frame: First 28 days of treatment ]
2. Part 1.1 (Dose Escalation): Proportion of participants who experience at least 1 DLT during the first 28 days of treatment. [ Time Frame: First 28 days of treatment ]
3. Part 1.1 (Dose Escalation): Cmax of STX-478 [ Time Frame: 12 months ]
4. Part 1.1 (Dose Escalation): AUC(0-inf) of STX-478 [ Time Frame: 12 months ]
5. Part 1.1 (Dose Escalation): AUC(0-t) of STX-478 [ Time Frame: 12 months ]
6. Part 1.1 (Dose Escalation): AUC(0-τ) of STX-478 [ Time Frame: 12 months ]
7. Part 1.1 (Dose Escalation): Change from baseline in ctDNA levels. [ Time Frame: 12 months ]
8. Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin [HbA1c] [ Time Frame: 12 months ]
9. Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose. [ Time Frame: 12 months ]
10. Part 1.1 (Dose Escalation): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide. [ Time Frame: 12 months ]
11. Part 1.1 (Dose Escalation): Objective response rate (ORR). [ Time Frame: 12 months ]
12. Part 1.1 (Dose Escalation): Incidence of TEAEs/SAEs ≥ grade 2. [ Time Frame: 12 months ]
13. Part 1.1 (Dose Escalation): Frequency of TEAEs according to CTCAE v5.0 criteria. [ Time Frame: 12 months ]
14. RP2D Selection (Parts 1.2-DS and 2.1): Cmax of STX-478 [ Time Frame: 12 months ]
15. RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-inf) of STX-478 [ Time Frame: 12 months ]
16. RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-t) of STX-478 [ Time Frame: 12 months ]
17. RP2D Selection (Parts 1.2-DS and 2.1): AUC(0-τ) of STX-478 [ Time Frame: 12 months ]
18. RP2D Selection (Parts 1.2-DS and 2.1): Change from baseline in ctDNA levels. [ Time Frame: 12 months ]
19. 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] [ Time Frame: 12 months ]
20. RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose. [ Time Frame: 12 months ]
21. RP2D Selection (Parts 1.2-DS and 2.1): Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide [ Time Frame: 12 months ]
22. Parts 1.2-DS and 2.1 (RP2D Selection): ORR [ Time Frame: 12 months ]
23. Parts 1.2-DS and 2.1 (RP2D Selection): Frequency counts and percentages of AEs based on MedDRA and CTCAE v5.0 [ Time Frame: 12 months ]
24. Parts 1.2-DS and 2.1 (RP2D Selection): Proportion of participants with DLTs. [ Time Frame: 12 months ]
25. Parts 1.2-DS and 2.1 (RP2D Selection): Change in ECOG performance status. [ Time Frame: 12 months ]
26. 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. [ Time Frame: 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
2. Has a new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen within 12 months prior to screening
3. 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.
4. Has at least 1 measurable tumor lesion per RECIST 1.1
5. Is ≥18 years of age at the time of signing the ICF
6. Has an ECOG performance status score of 0 or 1 at screening

Key Exclusion Criteria:

1. Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
2. Has symptomatic brain or spinal metastases
3. Has a tumor with mutations/deletions in PTEN and activating mutations in AKT or mTOR confirmed by a CLIA-certified laboratory
4. 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
5. Cohorts A0, A1, A2, A3, A4, and B: Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances.
6. 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
7. 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
8. Has had radiotherapy within 14 days before the initiation of study treatment

Contacts and Locations

Contacts

Contact: For questions concerning enrollment; Please email:; clinicaltrials@scorpiontx.com

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114-2696

Sponsors and Collaborators

Scorpion Therapeutics, Inc.

Investigators

• Study Director: Michael Streit, MD; Scorpion Therapeutics, Inc.

More Information

• Responsible Party: Scorpion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05768139
• Other Study ID Numbers: STX-478-101
• First Posted: March 14, 2023
• Last Update Posted: March 14, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Scorpion Therapeutics, Inc.:

Ovarian cancer; Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; HER2-negative breast cancer; HR-positive breast cancer; Gynecologic cancer; Endometrial cancer; Cervical cancer; Head and neck cancer; Head and neck squamous cell carcinoma; Fulvestrant; Antineoplastic Agents; PI3Kα; PI3K alpha; PI3Kα mutation; Alpelisib; STX-478; PI3Kα inhibitor; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Receptor Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Fulvestrant; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs