A Phase 1/2a Study of K-1728 in Advanced Solid Tumors (PIKYMA-01)

A First-in-Human Study of K-1728 Administered Alone and in Combination in Participants With Advanced or Metastatic Solid Tumors

This first-in-human, open-label, multicenter study evaluates K-1728 administered as monotherapy and in combination in participants with advanced or metastatic solid tumors. The study assesses the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of K-1728.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Neoplasms; Solid Tumors; PIK3CA Gene Mutation
• Intervention / Treatment: Drug: K-1728; Drug: Fulvestrant; Drug: Palbociclib

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Adults with advanced or metastatic solid tumors who are able to provide consent
• Documented activating PIK3CA mutation
• ECOG performance status 0 or 1
• Adequate organ function

Key Exclusion Criteria:

• Active or untreated central nervous system disease
• Clinical significant or uncontrolled cardiovascular disease
• Significant or uncontrolled intercurrent illness
• Pregnant or breastfeeding
• Other protocol-defined exclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: K-1728 Monotherapy; Participants receive K-1728 orally as monotherapy	Drug: K-1728; K-1728 will be administered orally once daily in 28-day cycles
Experimental: K-1728 + Endocrine Therapy; Participants receive K-1728 orally in combination with endocrine therapy	Drug: K-1728; K-1728 will be administered orally once daily in 28-day cycles; Drug: Fulvestrant; Fulvestrant will be administered intramuscularly on Days 1 and 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle
Experimental: K-1728 + Endocrine Therapy + CDK4/6 Inhibitor; Participants receive K-1728 orally in combination with endocrine therapy and a CDK4/6 inhibitor	Drug: K-1728; K-1728 will be administered orally once daily in 28-day cycles; Drug: Fulvestrant; Fulvestrant will be administered intramuscularly on Days 1 and 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle; Drug: Palbociclib; Palbociclib will be administered orally on Days 1-21 in 28-day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)/Maximum Efficacious Dose (MED) and Recommended Phase 2 Dose (RP2D)	Determination of the MTD/MED and RP2D of K-1728 administered as monotherapy and in combination	Cycle 1 (28 days) through completion of dose escalation (up to approximately 24 months)
Incidence of Dose-Limiting Toxicities (DLTs)	Number and percentage of participants experiencing a dose-limiting toxicity during the DLT-evaluation period with of K-1728 administered as monotherapy and in combination	Initiation of study drug through Cycle 1 (28 days)
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number and percentage of participants with adverse events and serious adverse events with K-1728 administered as a monotherapy and in combination	From first dose through 30 days after the last dose of study treatment (up to approximately 24 months)
Changes in laboratory parameters	Compared to baseline, changes in laboratory parameters with K-1728 administered as monotherapy and in combination	From first dose through 30 days after the last dose of study treatment (up to approximately 24 months)
Changes in vital signs	Compared to baseline, changes in vital signs with K-1728 administered as monotherapy and in combination	From first dose through 30 days after the last dose of study treatment (up to approximately 24 months)
Changes in electrocardiogram (ECG) parameters	Compared to baseline, changes in ECG parameters (including QT interval, QTc interval, QRS complex, and PR interval)	From first dose through 30 days after the last dose of study treatment (up to approximately 24 months)
Changes in physical examination	Compared to baseline, changes in physical examination	From first dose through 30 days after the last dose of study treatment (up to approximately 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Maximum Plasma Concentration (Cmax) of K-1728	Cmax of K-1728 when administered as monotherapy or in combination	Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle until end of treatment, approximately 24 months
Pharmacokinetics - Time to Maximum Plasma Concentration (Tmax) of K-1728	Tmax of K-1728 when administered as monotherapy or in combination	Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle until end of treatment, approximately 24 months
Pharmacokinetics - Area Under the Plasma Concentration-Time Curve (AUC) of K-1728	AUC of K-1728 when administered as monotherapy or in combination	Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle until end of treatment, approximately 24 months
Pharmacokinetics - Half-life (t1/2) of K-1728 when administered as monotherapy or in combination	t1/2 of K-1728 when administered as monotherapy or in combination	Approximately every 2 weeks in Cycle 1 (4-week cycle) and every cycle until end of treatment, approximately 24 months
Preliminary Efficacy - Overall Response Rate (ORR)	Objective Response Rate (ORR) as assessed by RECIST v1.1	Initiation of study drug until disease progression, assessed up to approximately 24 months

Collaborators and Investigators

• Sponsor: KymaThera, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: September 24, 2026
• First Submitted That Met QC Criteria: October 1, 2026
• First Posted (Actual): October 6, 2026

Study Record Updates

• Last Update Posted (Actual): October 6, 2026
• Last Update Submitted That Met QC Criteria: October 1, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; palbociclib
• Other Study ID Numbers: K-1728-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No