Recruiting

Phase 1

Phase 2

SpevatamigSpevatamig (PT886) as Monotherapy or in Combination With Chemo and/or ICI, for the Treatment of Patients With Advanced Gastric, Gastroesophageal Junction, Pancreatic Ductal or Biliary Tract Carcinomas (the TWINPEAK Study)

Sponsor:

Phanes Therapeutics

Code:

NCT05482893

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Pancreatic Ductal Adenocarcinoma

Biliary Tract Cancer (BTC)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Spevatamig (PT886)

Paclitaxel

Gemcitabine

Abraxane

KEYTRUDA® (pembrolizumab)

Study Details

Brief summary:

This is a first-in-human, Phase 1/2, open-label, dose escalation and dose expansion and combination study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Spevatamig (PT886). Patients with the following tumor types will be eligible for screening: unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, biliary tract carcinoma (BTC) and pancreatic ductal adenocarcinoma (PDAC).

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Pancreatic Ductal Adenocarcinoma

Biliary Tract Cancer (BTC)

Study ID

NCT05482893

Start date

Mar 15, 2023

Status verified date

Jul, 2026

Completion date

Apr, 2028

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria

1. 18 years or older and able to sign informed consent and comply with the protocol.
2. Measurable disease as defined by RECIST V1.1 criteria for solid tumors.
3. 3\. Part A and Part B: Histologically or cytologically confirmed unresectable advanced or metastatic solid gastric, gastroesophageal junction (GEJ), biliary tract or pancreatic carcinomas previously treated for advanced (metastatic or unresectable) disease or for which treatment is not available or not tolerated.

Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Patients who are HER2 positive are eligible.

Part C, substudy C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane).

Part C, substudy C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX.

Part C, substudy C4: Patients with m/a BTC who have progressed on 1L SOC chemotherapy (GemCis) ± ICI and are eligible for 2L SOC FOLFOX treatment.

Part D, substudy D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab).

Part D, substudy D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).
4. Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample (preferably fresh biopsy or if not possible, archival tissue) to be assessed for CLDN18.2 expression and other biomarkers.
5. ECOG performance status of 0 or 1.
6. Adequate organ function confirmed at screening and within 72 hours of initiating treatment.

Key Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:

1. Women who are pregnant or lactating.
2. Women of child-bearing potential (WOCBP) who do not use adequate birth control.
3. Has an active autoimmune disease that has required systemic treatment in the past 2 years.
4. Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents.

Additional inclusion and exclusion criteria will apply.

Study Design

Enrollment

258 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation

An accelerated titration design will be employed for early dose levels, followed by the standard 3+3 design at higher dose levels.

experimental: Dose Expansion

Two dose levels will be explored; the recommended dose for expansion (RDE) from Part A, and another dose level.

experimental: Combination Expansion with Chemotherapy

Part C, substudy C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel.

Part C, substudy C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane).

Part C, substudy C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX.

Part C, substudy C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6.

experimental: Combination Expansion with KEYTRUDA® (pembrolizumab)

Part D, substudy D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab).

Part D, substudy D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).

Interventions

Spevatamig (PT886)

Spevatamig (PT886) monotherapy, a novel bispecific antibody that targets Claudin 18.2 and CD47.

Paclitaxel

Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C1

Gemcitabine

Chemotherapy as a combination partner to Abraxane and Spevatamig (PT886) in Part C: substudy C2

Abraxane

Chemotherapy as a combination partner to Gemcitabine and Spevatamig (PT886) in Part C: substudy C2

KEYTRUDA® (pembrolizumab)

Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D.

FOLFOX

Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab, Part D only)

CAPOX

Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886)

FOLFIRINOX

Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudy C3

Primary outcome measure

To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy. [ Time Frame: Through study completion, an average of 2 years ]
To evaluate anti-tumor activity of PT886 as assessed by ORR, in Spevatamig (PT886) monotherapy and in each combination substudy. [ Time Frame: Through study completion. ]
To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy. [ Time Frame: Through study completion. ]

Central Contacts and Locations

Central contacts

Phanes Therapeutics

858-766-0852 clinical-trials@phanestx.com

Locations

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Recruiting

Duarte, California, United States, 91010

USC Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Sarah Cannon Research Institute (SCRI)

Recruiting

Denver, Colorado, United States, 80218

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Norton Cancer Institute

Recruiting

Louisville, Kentucky, United States, 40202

Duke Cancer Center

Recruiting

Durham, North Carolina, United States, 27710

University of Pittsburgh Medical Center (UPMC)

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

MD Anderson Cancer Center, GI Medical Oncology Dept

Recruiting

Houston, Texas, United States, 77030

NEXT Oncology

Recruiting

Fairfax, Virginia, United States, 22031

University of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

More Information

Sponsor

Phanes Therapeutics

Last update posted

Jul 9, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Phanes Therapeutics on 2026-07-09.