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)

Phanes Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: CAPOX; Drug: FOLFIRINOX; Drug: Paclitaxel; Drug: Abraxane; Drug: FOLFOX; Drug: KEYTRUDA® (pembrolizumab); Drug: Gemcitabine; Drug: Spevatamig (PT886)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05482893

PT886X1101

KEYNOTE-F58 (MK-3475-F58) (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 258 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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258 participants in 4 patient groups

Dose Escalation

Experimental group

Description:

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

Treatment:

Drug: Spevatamig (PT886)

Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: Spevatamig (PT886)

Combination Expansion with Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Spevatamig (PT886)

Drug: FOLFOX

Drug: Abraxane

Drug: Paclitaxel

Drug: FOLFIRINOX

Combination Expansion with KEYTRUDA® (pembrolizumab)

Experimental group

Description:

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).

Treatment:

Drug: Spevatamig (PT886)

Drug: KEYTRUDA® (pembrolizumab)

Drug: FOLFOX

Drug: CAPOX