Spevatamig (PT886) as Monotherapy or in Combination With Chemo and/or Targeted Therapy and/or ICI, for the Treatment of Patients With Advanced Gastrointestinal Cancers, Including 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: 350
• 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), pancreatic ductal adenocarcinoma (PDAC) and colorectal carcinoma (CRC).

Conditions

Biliary Tract Cancer (BTC); Gastric or Gastroesophageal Junction Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• To evaluate the safety and tolerability of Spevatamig (PT886) as monotherapy and in each individual combination substudy.

  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.

  Through study completion.

• To determine the recommended dose for expansion of Spevatamig (PT886) monotherapy.

  Through study completion.

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

• To evaluate anti-tumor activity as assessed by additional measures other than ORR, in Spevatamig (PT886) monotherapy and in each combination substudy.

  Through study completion, an average of 2 years

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

One or more indications (GC/GEJC, BTC, CRC or PDAC) and/or lines of treatment may be selected for dose expansion at two dose levels (RDE1 and RDE2).

Drug: Spevatamig (PT886)

Combination Expansion with Chemotherapy or Targeted Therapy

EXPERIMENTAL

Part C, substudy C1: patients with 2L m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with Paclitaxel. Part C, substudy C2: patients with 1L m/a PDAC will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane). Part C, substudy C3: patients with 1L m/a PDAC will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX or NALIRIFOX. Part C, substudy C4: patients with 2L BTC will receive PT886 in combination with SOC chemotherapy mFOLFOX6. Part C, substudy C5: patients with 3L CRC patients will receive PT886 in combination with SOC chemotherapy TAS-102. Part C, substudy C6: patients with 3L CRC patients will receive PT886 in combination with bevacizumab. Part C, substudy C7: patients with 3L CRC patients will receive PT886 in combination with SOC chemotherapy TAS-102 and bevacizumab.

Drug: Spevatamig (PT886); Drug: Paclitaxel; Drug: Gemcitabine; Drug: Abraxane; Drug: FOLFOX; Drug: FOLFIRINOX; Drug: TAS 102; Drug: Bevacizumab; Drug: NALIRIFOX

Combination Expansion with KEYTRUDA® (pembrolizumab)

EXPERIMENTAL

Part D, substudy D2: patients with 1L BTC will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab) and standard of care chemotherapy GemCis. Part D, substudy D3: patients with 2L or 3L m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab). Part D, substudy D4: patients with 1L HER2 negative m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).

Drug: Spevatamig (PT886); Drug: KEYTRUDA® (pembrolizumab); Drug: FOLFOX; Drug: CAPOX; Drug: Gemcitabine Combined With Cisplatin

Interventions

Spevatamig (PT886) DRUG

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

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

Paclitaxel DRUG

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

Combination Expansion with Chemotherapy or Targeted Therapy

Gemcitabine DRUG

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

Combination Expansion with Chemotherapy or Targeted Therapy

Abraxane DRUG

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

Combination Expansion with Chemotherapy or Targeted Therapy

FOLFOX DRUG

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

Combination Expansion with Chemotherapy or Targeted Therapy; Combination Expansion with KEYTRUDA® (pembrolizumab)

CAPOX DRUG

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

Combination Expansion with KEYTRUDA® (pembrolizumab)

KEYTRUDA® (pembrolizumab) DRUG

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

Combination Expansion with KEYTRUDA® (pembrolizumab)

FOLFIRINOX DRUG

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

Combination Expansion with Chemotherapy or Targeted Therapy

TAS 102 DRUG

Chemotherapy as a combination partner to Spevatamig (PT886) in Part C: substudies C5 and C7.

Combination Expansion with Chemotherapy or Targeted Therapy

Bevacizumab DRUG

Targeted therapy as a combination partner to Spevatamig (PT886) in Part C: substudies C6 and C7.

Combination Expansion with Chemotherapy or Targeted Therapy

Gemcitabine Combined With Cisplatin DRUG

Chemotherapy as a combination partner to Spevatamig (PT886) and KEYTRUDA® (pembrolizumab) in Part D: substudy D2

Combination Expansion with KEYTRUDA® (pembrolizumab)

NALIRIFOX DRUG

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

Combination Expansion with Chemotherapy or Targeted Therapy

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: 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 B: Patients with PDAC and GC/GEJC must meet the same criteria as those in Part A depending on which indication and line of treatment are chosen for expansion. Patients considered 2L with BTC, without actionable genomic mutations. Patients considered 3L with CRC.
• Part C, substudy C1: patients with 2L m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with Paclitaxel. Patients who are HER2 positive are eligible.
• Part C, substudy C2: patients with 1L m/a PDAC will receive Spevatamig (PT886) in combination with Gemcitabine plus nab-Paclitaxel (Abraxane).
• Part C, substudy C3: patients with 1L m/a PDAC will receive Spevatamig (PT886) in combination with Gemcitabine plus FOLFIRINOX/mFFX or NALIRIFOX.
• Part C, substudy C4: Patients with m/a BTC without actionable genomic mutations who have progressed on 1L SOC chemotherapy (GemCis) ± ICI and are eligible for 2L SOC FOLFOX treatment.
• Part C, substudy C5 and C7: Patients with CRC who are considered 3L, TAS-102 treatment naïve, eligible to receive 3L SOC TAS-102 treatment, and able to swallow oral tablets.
• Part C, substudy C6 and C7: Patients with CRC who are considered 3L, and eligible to receive bevacizumab treatment, with no contraindication to bevacizumab
• Part D, substudy D2: patients with m/a BTC with adenocarcinoma histology only, who are treatment naïve for their m/a disease and are eligible for treatment with SOC chemotherapy and ICI.
• Part D, substudy D3: patients with 2L or 3L m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with KEYTRUDA® (pembrolizumab).
• Part D, substudy D4: patients with 1L HER2 negative m/a GC/GEJ-C will receive Spevatamig (PT886) in combination with SOC chemotherapy and KEYTRUDA® (pembrolizumab).
• 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.
• 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.
• Prior CLDN18.2 or CD47 targeting therapies, or SIRPα (signal regulatory protein alpha) targeting agents.

Sponsors & Collaborators

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

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; Colorectal Neoplasms

Interventions

Paclitaxel; Gemcitabine; Albumin-Bound Paclitaxel; pembrolizumab; Folfox protocol; folfirinox; trifluridine tipiracil drug combination; Bevacizumab; Cisplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal 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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

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: September 28, 2026

Record last verified: 2026-09

Locations

US (11)