Spevatamig (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)

NCT05482893 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: PT886X1101KEYNOTE-F58 (MK-3475-F58)
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 11

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)

Outcome Measures

Primary Outcomes (3)

• To determine the dose-limiting toxicity (DLT) of Spevatamig (PT886).

  Through study completion.

• To determine the maximum tolerated dose (MTD) of Spevatamig (PT886).

  Through study completion.

• To evaluate the safety and tolerability of Spevatamig (PT886).

  Through study completion, an average of 2 years

Secondary Outcomes (3)

• To evaluate the pharmacokinetics of Spevatamig (PT886).

  Through study completion, an average of 2 years

• To evaluate the immunogenicity (ADA) of Spevatamig (PT886).

  Through study completion, an average of 2 years

• Preliminary Efficacy of Spevatamig (PT886).

  Through study completion.

Study Arms (4)

Dose Escalation

EXPERIMENTAL

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

Drug: Spevatamig (PT886)

Dose Expansion

EXPERIMENTAL

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

Drug: Spevatamig (PT886)

Combination Expansion with Chemotherapy

EXPERIMENTAL

Part C, Cohort C1: 2L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX. Part C, Cohort C4: 2L BTC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Cohort C5, 1L HER2 negative PD-L1 CPS \< 1 GC/GEJC patients will receive PT886 in combination with SOC chemotherapy mFOLFOX6 or CAPOX.

Drug: Spevatamig (PT886); Drug: Paclitaxel; Drug: Gemcitabine; Drug: Abraxane; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Drug: Capecitabine; Drug: FOLFIRINOX

Combination Expansion with KEYTRUDA® (pembrolizumab)

EXPERIMENTAL

Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).

Drug: Spevatamig (PT886); Drug: KEYTRUDA® (pembrolizumab); Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Drug: Capecitabine

Interventions

Spevatamig (PT886) DRUG

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

Combination Expansion with Chemotherapy; Combination Expansion with KEYTRUDA® (pembrolizumab); Dose Escalation; Dose Expansion

Paclitaxel DRUG

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

Combination Expansion with Chemotherapy

Gemcitabine DRUG

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

Combination Expansion with Chemotherapy

Abraxane DRUG

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

Combination Expansion with Chemotherapy

KEYTRUDA® (pembrolizumab) DRUG

Immune checkpoint inhibitor as a combination partner to Spevatamig (PT886) in Part D: Cohort D2, D3 and D4.

Combination Expansion with KEYTRUDA® (pembrolizumab)

Oxaliplatin DRUG

Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4

Combination Expansion with Chemotherapy; Combination Expansion with KEYTRUDA® (pembrolizumab)

Leucovorin DRUG

Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4

Combination Expansion with Chemotherapy; Combination Expansion with KEYTRUDA® (pembrolizumab)

Fluorouracil DRUG

Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4

Combination Expansion with Chemotherapy; Combination Expansion with KEYTRUDA® (pembrolizumab)

Capecitabine DRUG

Chemotherapy as a combination partner to KEYTRUDA® (pembrolizumab) and Spevatamig (PT886) in Part D: Cohort D4

Combination Expansion with Chemotherapy; Combination Expansion with KEYTRUDA® (pembrolizumab)

FOLFIRINOX DRUG

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

Combination Expansion with Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older and able to sign informed consent and comply with the protocol.
• Measurable disease as defined by RECIST V1.1 criteria for solid tumors.
• \. 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, Cohort 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, Cohort C2: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane).
• Part C, Cohort C3: 1L m/a PDAC patients will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX.
• Cohort C4: Patients with m/a BTC who have progressed on 1L SOC chemotherapy (GemCis) ± ICI and are eligible for 2L SOC FOLFOX treatment.
• Cohort C5: Patients with m/a HER2 negative GC/GEJC and present a PD-L1 CPS score of \<1%, who are treatment naïve for their m/a disease and eligible for treatment with SOC chemotherapy (mFOLFOX6 or CAPOX).
• Part D, Cohort D2: Patients with m/a GC/GEJ-C, that have progressed under 1L SOC chemotherapy, and zolbetuximab, will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab).
• Part D, Cohort D3: 2L or 3L m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab).
• Part D, Cohort D4: 1L HER2 negative m/a GC/GEJ-C patients will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).
• Biopsies:
• 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.
• Parts C and D: Patients must present with ≥ 10%; ≥ 2+ CLDN18.2 positive TC in their tumor tissue.
• ECOG performance status of 0 or 1.

You may not qualify if:

• Patients are excluded from the study if any of the following criteria apply:
• Women who are pregnant or lactating.
• Women of child-bearing potential (WOCBP) who do not use adequate birth control.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to study treatment.
• Patients with a history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or have a history of interstitial lung disease. History of COVID-19 pneumonia with fibrotic changes.
• Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases).
• Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents. For Part D, Cohort D2, prior treatment with zolbetuximab is allowed.
• Impaired cardiac function or significant diseases.
• Prior hemolytic anemia or Evans Syndrome in the last 3 months.
• Active gastric perforation, pyloric obstruction, complete biliary obstruction, complete or incomplete intestinal obstruction requiring clinical intervention, or pleural effusion or peritoneal effusion requiring clinical intervention.
• Patients who have experienced any thromboembolic event such as deep vein thrombosis (DVT) or pulmonary embolism in the past 6 months.

Sponsors & Collaborators

• Phanes Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (11)

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

Duarte, California, 91010, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Sarah Cannon Research Institute (SCRI)

Denver, Colorado, 80218, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

RECRUITING

Dana-Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

Duke Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MD Anderson Cancer Center, GI Medical Oncology Dept

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

Fairfax, Virginia, 22031, United States

RECRUITING

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Paclitaxel; Gemcitabine; Albumin-Bound Paclitaxel; pembrolizumab; Oxaliplatin; Leucovorin; Fluorouracil; Capecitabine; folfirinox

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Phanes Therapeutics

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: August 1, 2022
• Study Start: March 15, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: November 4, 2025

Record last verified: 2025-06

Locations

US (11)