Curated by Fight CRC’s Medical Advisory Board & Research Advocacy Training and Support (RATS) team. 

If your colorectal cancer tests HER2-positive (IHC 3+ or IHC 2+ with ISH+) and RAS wild-type, you may have targeted therapy options. This month’s roundup highlights trials that prioritize outcomes, side‑effect management, and patient‑reported measures. 

While these trials may not be right for everyone or may not be open at your treatment center, any that seem relevant to your diagnosis could be worth discussing with your care team.

• Recruitment Status: Recruiting (50+ global sites) 
• Phase / Sites: Randomized Phase 3 (50+ international sites) 
• Stage: Primarily Stage IV (metastatic); also includes locally advanced unresectable
  CRC (Stage IIIc) 
• What it’s studying: Tests tucatinib + trastuzumab with chemotherapy (FOLFOX) as first‑line therapy for HER2+, RAS wild‑type mCRC or unresectable disease. 
• Why it matters: Builds on MOUNTAINEER I/II showing durable responses; could move HER2 targeting into standard first‑line care. 
• ClinicalTrials.gov: clinicaltrials.gov/study/NCT05253651 
• Reference: Strickler, J. H., et al. (2023). Tucatinib plus trastuzumab for HER2‑positive mCRC. The Lancet Oncology. 

Patient Tip: Newly diagnosed with HER2+ metastatic CRC? Ask if this trial is open near you.

• Recruitment Status: Completed 
• Phase / Sites: Randomized Phase 2 (20+ sites across U.S., Europe, and Asia) 
• Stage: Stage IV (metastatic colorectal cancer only) 
• What it’s studying: Compares lower (5.4 mg/kg) vs. standard dosing of T‑DXd to reduce nausea and risk of ILD while maintaining benefit. 
• Why it matters: Aims for safer dosing with similar efficacy to support long‑term treatment. 
• ClinicalTrials.gov: clinicaltrials.gov/study/NCT04744831 
• Reference: Raghav, K., et al. (2024). Trastuzumab deruxtecan in HER2‑positive mCRC (DESTINY‑CRC02). The Lancet Oncology. 

Patient Tip: On or considering T‑DXd? Ask about reduced‑dose options and lung‑symptom monitoring. 

• Recruitment Status: Unknown (previously active, not recruiting) 
• Phase / Sites: Single-arm Phase 2 (European academic centers) 
• Stage: Stage IV (metastatic only) 
• What it’s studying: Evaluates T‑DM1 + pertuzumab after prior HER2 therapy in HER2+ mCRC. 
• Why it matters: Showed disease control with low toxicity; may suit patients post other HER2 therapies. 
• ClinicalTrials.gov: clinicaltrials.gov/study/NCT03225937 
• Reference: Sartore‑Bianchi, A., et al. (2020). Dual HER2 targeting in mCRC: HERACLES experience. Annals of Oncology. 

Patient Tip: Treated in Europe and finished prior HER2 therapy? Ask about access programs or follow‑up studies. 

• Recruitment Status: Active, not recruiting (U.S. multi‑center) 
• Phase / Sites: Randomized Phase 2 (U.S.100+ sites)  
• Stage: Stage IV only (metastatic colorectal cancer) 
• What it’s studying: Compares dual HER2 antibodies with standard EGFR‑based chemotherapy in HER2+ mCRC. 
• Why it matters: Seeks similar tumor control with fewer high‑grade toxicities; high HER2 gene copy number may predict benefit.  
• ClinicalTrials.gov: clinicaltrials.gov/study/NCT03365882 
• Reference: Meric‑Bernstam, F., et al. (2023). SWOG S1613 results (abstract). Journal of Clinical Oncology. 

Patient Tip: If you’ve had ≥1 prior chemo regimen, ask whether your HER2 testing reports gene copy number.

• Recruitment Status: Recruiting (MSK, NY/NJ) 
• Phase / Sites: Single-arm, Phase 2 (Memorial Sloan Kettering, 7 locations in NY and NJ) 
• Stage: Stage II/III (non-metastatic, locally advanced rectal cancer) 
• What it’s studying: Uses tucatinib + trastuzumab before and during CAPOX/FOLFOX to shrink tumors earlier in HER2+/RAS WT rectal cancer. 
• Why it matters: Could improve the chance for organ preservation or less extensive surgery. 
• ClinicalTrials.gov: clinicaltrials.gov/study/NCT05672524 
• Reference: Memorial Sloan Kettering Cancer Center. (2025). ClinicalTrials.gov record for NCT05672524. 

Patient Tip: Newly diagnosed HER2+/RAS wild‑type rectal cancer? Ask about eligibility at MSK. 

Targeted therapies that block EGFR or HER2 can cause skin rashes. Preventing rash early helps you stay on treatment and feel better during therapy. 

• Start oral doxycycline 100 mg twice daily or minocycline 100 mg daily on Day 1. 
• Use mild steroid cream (hydrocortisone 1%) on the face and upper torso. 
• Apply SPF 30+ sunscreen daily; choose gentle cleansers and moisturizers. 
• Ask for early dermatology support if rash worsens. 

Selected references (APA): 

Melosky, B., et al. (2009). Management of skin rash during EGFR‑targeted monoclonal antibody treatment for GI malignancies: Canadian recommendations. Current Oncology, 16(1), 16–26. [Link: Management of Skin Rash during egfr-Targeted Monoclonal Antibody Treatment for Gastrointestinal Mal…]

Hofheinz, R. D., et al. (2016). Recommendations for the prophylactic management of skin reactions from EGFR inhibitors. The Oncologist, 21(12), 1483–1491. [LINK: Recommendations for the Prophylactic Management of Skin Reactions Induced by Epidermal Growth Facto…]

Belum, V. R., et al. (2013). Dermatologic adverse events in lower GI cancers: Management strategies. Current Treatment Options in Oncology, 14, 389–404. [LINK: Dermatologic Adverse Events to Targeted Therapies in Lower GI Cancers: Clinical Presentation and Ma…]

Disclaimer: This content is for informational purposes only and is not medical advice. Talk with your oncology team about testing, treatment options, clinical trial eligibility, and side‑effect management.

• Recruitment Status: 
  • Phase 1 (NCT05029882): Completed / no longer recruiting (7–10 dose escalation + ~85–95 expansion sites, multiple cancer types) 

• • Phase 2 (NCT06107413): Recruiting internationally (~65 global sites) 

• What It’s Studying: ABBV-400 is a c-Met–targeted ADC delivering a TOP1 inhibitor payload. 

• • Phase 1: Established safety, dosing, and early activity across multiple cancers including CRC. 

• • Phase 2: Testing ABBV-400 with FOLFOX and bevacizumab in previously treated mCRC. 

• ClinicalTrials.gov: NCT05029882 | NCT06107413 

• Study Overview (ASCO): 

• • Raghav, K. et al. (2023). Dose escalation results, ASCO Annual Meeting Abstract. 

• • Early Phase 2 data: promising response rates, manageable safety. 

• Learn More: Onclive – Dr. Raghav 

Patient Tip:  If you have c-Met–positive mCRC, ask about eligibility for ongoing Phase 2 or 3 ABBV-400 studies now open.

• Recruitment Status: Recruiting (NCT06614192) 

• Phase / Sites: Phase 3 (51 international sites) 

• What It’s Studying: ABBV-400 vs trifluridine/tipiracil (LONSURF) plus bevacizumab in refractory mCRC. 

• ClinicalTrials.gov: NCT06614192 

• Study Overview (ASCO 2025): Strickler, J. et al. Telisotuzumab adizutecan in c-Met–expressing refractory mCRC (Abstract TPS3635). 

• Learn More: VJ Oncology – ASCO 25 Interview 

Patient Tip: If you’ve already had LONSURF + bevacizumab, ask your oncologist whether this trial’s design applies to you or whether ABBV-400 might be available through other studies. 

• Recruitment Status: Early-phase research (Nature publication, Aug 2024) 

• Phase / Sites: Early-phase clinical trial, academic centers (~10–15 estimated) 

• What It’s Studying: Next-generation ADCs for CRC, focusing on enhanced delivery of TOP1 inhibitor payloads to tumor sites. 

• ClinicalTrials.gov: Not registered – see below to learn more 

• Learn More: Nature – PROCEADE-CRC  

Patient Tip: These novel ADCs are still early in development. If considering ADC trials, ask your doctor about eligibility restrictions (e.g., prior ADC exposure). 

• Recruitment Status: Opening Nov 2025 (Canada, France, UK) – not enrolling in the US 

• Phase / Sites: Phase 3 (30–40 international sites) 

• What It’s Studying: Phase 3 trial testing BOT/BAL therapy in metastatic solid tumors. 

• ClinicalTrials.gov: Pending registration 

Patient Tip: If you live outside the US, particularly in Canada, France, or the UK, ask whether this trial is opening near your region in late 2025. 

• Recruitment Status: Recruiting / planned (4 U.S. centers; MDA MRD trial opens Feb 2026; NCT07136077 not yet recruiting) 

• Phase / Sites: 

• • Fruquintinib + chemo / immunotherapy / bevacizumab: Phase 2 (multi-center, ~10–20 U.S. sites) 

• • Fruquintinib + I/O in MRD: Phase 2 (MDA, single-site, Feb 2026) 

• • Fruquintinib + Tislelizumab (NCT07136077): Phase 2 (1 site, not yet recruiting) 

• What It’s Studying: Fruquintinib is being tested in multiple combinations for colorectal cancer: 

• • Fruquintinib + chemotherapy 

• • Fruquintinib + immunotherapy (I/O) – includes Tislelizumab trial (NCT07136077) 

• • Fruquintinib + bevacizumab 

• • Fruquintinib + I/O in MRD (MDA-led trial, Feb 2026) 

• ClinicalTrials.gov: Search Fruquintinib CRC Trials | NCT07136077 

• Study Overview: Fruquintinib is FDA-approved as monotherapy; these trials are testing whether combinations can expand benefit, especially in MSS CRC. 

• Learn More: Fight CRC programming with Dr. Cathy Eng 

Patient Tip: If you have MSS CRC, ask whether you may qualify for combination studies — especially Fruquintinib + immunotherapy. 

• Recruitment Status: Recruiting/planned 

• Phase / Sites: Phase 1/2 (multi-country: U.S., EU, APAC; ~15–25 sites) 

• What It’s Studying:  

• • Dr. Marwan Fakih (City of Hope): TP53-targeted trial 

• • Dr. David Hong (MDA): Pynacle trial 

• • Dr. Nicholas Klemen (NIH): Cellular therapy trial 

• ClinicalTrials.gov: Multiple active listings – search “TP53 colorectal cancer” or check individual trials 

• Learn More: Contact investigators directly 

• • Dr. Marwan Fakih (City of Hope): TP53-targeted trial (contact: mfakih@coh.org) 

• • Dr. David Hong (MDA): Pynacle trial (multi-site) 

• • Dr. Nicholas Klemen (NIH): Cellular therapy trial (contact: nicholas.klemen@nih.org) 

Patient Tip: Ask if your tumor has TP53 hotspot mutations; these trials are early, but could offer a new treatment path for patients with limited standard options. 

• Recruitment Status: Completed (Australian New Zealand Clinical Trials Registry: ACTRN12615000381583) 

• Phase / Sites: Phase 2 randomized (22 sites in Australia) 

• What It’s Studying: Compared ctDNA-guided chemo vs standard decisions in Stage II colon cancer. 

• ClinicalTrials.gov: NCT03437501 

• Study Overview: Tie, J. et al. (2022). NEJM. ctDNA guidance reduced chemo use by 28% without compromising recurrence-free survival. 

• Learn More: Read The Full Article: NEJM – DYNAMIC Study 

Patient Tip: If you were Stage II, ask your oncologist if you’ve had ctDNA testing, which may help avoid unnecessary chemotherapy. 

• Recruitment Status: Recruiting 

• Phase / Sites: GALAXY: observational, VEGA + ALTAIR: Phase 3 (~150 sites in Japan 1 outside Japan) 

• What It’s Studying: 

• • GALAXY: Observational registry tracking recurrence risk via ctDNA 

• • VEGA: De-escalation trial—omitting chemo if ctDNA-negative 

• • ALTAIR: Escalation trial—adding therapy if ctDNA-positive 

• Learn More: GALAXY Study – AACR. Publication: Nakamura, Y. et al. (2025). Clinical Cancer Research, 31(2), 328–337.

Patient Tip: If you are ctDNA-positive post-surgery, these trials are shaping the next generation of adjuvant care. 

• Recruitment Status: Recruiting (NCT05174169) 

• Phase / Sites: Phase 2/3 (~1,600 patients planned, multi-center across U.S. & Canada) 

• What It’s Studying: Using ctDNA after surgery to guide chemotherapy for Stage III or high-risk Stage II colon cancer patients. 

• ClinicalTrials.gov: NCT05174169 

• Study Overview: U.S. arm of the global CIRCULATE platform, evaluating whether ctDNA can guide escalation/de-escalation decisions.

Patient Tip: Ask your care team if you are eligible for CIRCULATE-US, as it’s one of the largest North American ctDNA-guided adjuvant trials. 

*Featured ‘Key ctDNA Trials To Know’ for September Hot Topic Clinical Trials.

• Biomarker Focus: BRAF V600E–mutant metastatic CRC
• Recruitment Status: Not recruiting (NCT04607421)
• What It’s Studying: A targeted therapy and chemotherapy combination for newly diagnosed metastatic CRC with BRAF V600E
• ClinicalTrials.gov: NCT04607421
• Study Overview (ASCO): Kopetz, S. et al. (2025). Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nature Medicine.
  Read The Full Article Here

Patient Tip: If you have the BRAF V600E mutation, ask your oncologist whether recent results from this trial might apply to your treatment options.

• Biomarker Focus: BRAF V600E–mutant metastatic CRC
• Recruitment Status: Not recruiting (NCT04607421)
• What It’s Studying: A targeted therapy and chemotherapy combination for newly diagnosed metastatic CRC with BRAF V600E
• ClinicalTrials.gov: NCT04607421
• Study Overview (ASCO): Kopetz, S. et al. (2025). Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nature Medicine.
  Read The Full Article Here

Patient Tip: If you have the BRAF V600E mutation, ask your oncologist whether recent results from this trial might apply to your treatment options.

• Biomarker Focus: Microsatellite Stable (MSS) metastatic CRC
• Recruitment Status: Some studies still recruiting (Search ClinicalTrials.gov by drug names)
• Study Overview: A novel combination of two immune checkpoint inhibitors, sometimes with chemotherapy, for patients with MSS CRC. This includes the first-line BBOPCO trial at Duke and smaller studies combining Botensilimab + Balstilimab with other treatments.
• ClinicalTrials.gov: Search Botensilimab OR Balstilimab
• Notable trial: BBOPCO trial (first-line, MSS CRC, at Duke). No centralized link exists—must be searched by drug/trial name.

Patient Tip: If you’ve been told you have MSS CRC and immunotherapy hasn’t been part of your care, this combination might offer a new approach. Ask if you’re eligible for one of the enrolment trials.

• Biomarker Focus: KRAS or BRAF mutations (G12C excluded)
• Recruitment Status: Recruiting (NCT06445062)
• What It’s Studying: A multi-target drug that blocks multiple cancer-driving proteins, including KRAS and BRAF
• ClinicalTrials.gov: NCT06445062
• Study Overview: Jiang, J. et al. (2024). Translational and therapeutic evaluation of RAS-GTP inhibition by RMC-6236 in RAS-driven cancers. Cancer Discovery, 14(6), 994–1010.
  Read the Full Article Here

Patient Tip: If your cancer has a KRAS or BRAF mutation and you’ve already gone through standard therapies, this may be an option to explore—especially if you’re open to early-phase trials.

Advocate Note: KRAS G12D mutations are now a major research focus, with over 16 active U.S. trials as of July 31, 2025. KRAS mutations are found in ~40% of mCRC cases, and KRAS G12D accounts for ~15% of all mCRC. View trials here.

• Biomarker Focus: BRAF Class II/III and other RAF/RAS alterations
• Recruitment Status: Recruiting (NCT06270082)
• What It’s Studying: A targeted therapy that acts as a “molecular glue” to disrupt abnormal signaling in tumors with non-V600E BRAF or RAS mutations
• ClinicalTrials.gov: NCT06270082
• Study Overview: Li, J. et al. (2024). Kinase inhibitors and kinase-targeted cancer therapies: recent advances and future perspectives. Int J Mol Sci, 25(10), 5489. Read the Full Article Here

Patient Tip: If you’ve been told your mutation is “non-V600E” BRAF or a RAS alteration, this might be one of the few trials focused specifically on your tumor type.

• Biomarker Focus: BRAF V600E–mutant CRC
• Recruitment Status: Recruiting (NCT06102902)
• What It’s Studying: Combines a new epigenetic drug with a known targeted therapy pair to see if it can further improve tumor response
• ClinicalTrials.gov: NCT06102902
• Study Overview: Gu, R. et al. (2024). A comprehensive overview of the molecular features and therapeutic targets in BRAFV600E-mutant colorectal cancer. Clin Transl Med.
  Read the Full Article Here

Patient Tip: If you’ve already tried a targeted BRAF therapy and are looking for next steps, this trial may offer a new approach. It’s early-phase, so ask about safety and eligibility.

• Biomarker Focus: MSS CRC, possibly BRAF mutation
• Recruitment Status: Not recruiting (NCT03388190)
• What It’s Studying: Combines a short chemotherapy regimen with immunotherapy to see if it improves immune response in MSS patients
• ClinicalTrials.gov: NCT03388190
• Study Overview: Ree, A.H. et al. (2024). First-line oxaliplatin-based chemotherapy and nivolumab for metastatic microsatellite-stable colorectal cancer—the randomized METIMMOX trial. Br J Cancer.
  Read the Full Article Here

Patient Tip: This trial has completed enrollment, but if you’re MSS and exploring immunotherapy, your oncologist might consider similar strategies based on this trial’s findings.

Disclaimer: Inclusion in this list does not imply endorsement or guaranteed benefit. Always consult your healthcare provider to determine if a clinical trial is appropriate for you.